CHAPTER-2

BIODYNAMIC AGRICULTURE
Biodynamic agriculture is a form of alternative agriculture very similar
to organic farming, but it includes various esoteric concepts drawn from
the ideas of Rudolf Steiner (1861–1925). Initially developed in 1924, it
was the first of the organic agriculture movements. It treats soil fertility,
plant growth, and livestock care as ecologically interrelated
tasks, emphasizing spiritual and mystical perspectives.
Biodynamic has much in common with other organic approaches – it
emphasizes the use of manures and composts and excludes the use of
artificial chemicals on soil and plants. Methods unique to the
biodynamic approach include its treatment of animals, crops, and soil as
a single system, an emphasis from its beginnings on local production
and distribution systems, its use of traditional and development of new
local breeds and varieties. Some methods use an astrological sowing and
planting calendar. Biodynamic agriculture uses various herbal and
mineral additives for compost additives and field sprays; these are
prepared using methods that are more akin to sympathetic
magic than agronomy, such as burying ground quartz stuffed into the
horn of a cow, which are said to harvest "cosmic forces in the soil."
As of 2016 biodynamic techniques were used on 161,074 hectares in 60
countries. Germany accounts for 45% of the global total; the remainder
average 1750 ha per country. Biodynamic methods of cultivating
grapevines have been taken up by several notable vineyards. There are
certification agencies for biodynamic products, most of which are
members of the international biodynamic standards group Demeter
International.
No difference in beneficial outcomes has been scientifically established
between certified biodynamic agricultural techniques and similar organic
and integrated farming practices. Biodynamic agriculture lacks strong
scientific evidence for its efficacy and has been labeled
a pseudoscience because of its overreliance upon esoteric knowledge
and mystical beliefs.

2.1Good agricultural practices in cultivation of medicinal plants

including Organic farming
India has a rich heritage of plant based healthcare systems like
Ayurveda, Unani and Siddha with a very high degree of societal
acceptance. There is a global upsurge in the use of traditional and
complementary systems of medicine. This is primarily due to the fact
that these systems of medicine, being largely plant based, are generally
safe, efficacious and affordable. The increasing demand of
natural/herbal products world over, therefore, creates a need not only for
conserving medicinal plants in-situ but also their cultivation outside the
forest areas in public and private lands. Forests have been the main
source of the raw material used in the manufacture of Ayurveda, Siddha
and Unani medicines. But concerned has been raised that unsustainable
collection from the wild has resulted in a large number of species
entering the red data book. The Department of AYUSH, through the
schemes of the National Medicinal Plants Board (NMPB), has launched
major initiatives to promote cultivation of medicinal plants and thereby
integrate medicinal plants into the farming systems. The major
challenges facing growth and outreach of the traditional/herbal
medicinal products are their quality, safety and efficacy. This inter-alias
is dependent on the quality of the raw material used in the manufacture
of the finished product. The National Medicinal Plants Board (NMPB),
Department of AYUSH has prepared India specific guidelines on Good
Agriculture Practices (GAPs) on the pattern of Good Agriculture and
Field Collection Practices (GACPs) developed by the World Health
Organization (WHO) for medicinal plants. In the preparation of this
standard assistance has been taken from Good Agriculture and
Collection Practices (GACPs) developed by the World Health
Organization (WHO) in 2003 and Good Agricultural Practices
enunciated by the GLOBALGAP Secretariat which is being
implemented in over 80 countries. The requirements given in this
standard are subject to the following statutory and regulatory provisions-
a. The Drugs and Cosmetics Act and Rules (as amended up through 30th
June 2005. New Delhi: Department of Health. 2005. Schedule T: Good
Manufacturing Practices (GMPs) for Ayurveda, Siddha and Unani
Medicines.
b. The Ayurvedic Pharmacopoeia of India, 5 Volumes, Ministry of
Health and Family Welfare, Govt. of India, New Delhi, 1989-2005
c. The Siddha Pharmacopoeia of India, Part I (1), Ministry of Health and
Family Welfare, Govt. of India, New Delhi, 2007.
d. The Unani Pharmacopoeia of India, Part-I, Ministry of Health and
Family Welfare, Govt. of India, New Delhi In preparation of this
standard.

2.2 Pest and Pest management in medicinal plants

Pest
In the plant world, pests refer to harmful organisms that latch on to
plants, rendering them unsuitable for harvest. While most of these
organisms tend to be insects, some fungi or plants can also be classified
as pests. Every garden is prone to pests. Some organisms are harmless
but the majorities are detrimental to a plant’s roots, leaves, and overall
health. This is why it is important to carefully prune plants and adopt the
necessary precautions for proper pest control.
Pest management
Effective pest management depends on the accurate identification of
the pest. Insects and mites often are associated with specific plants,
and they follow certain development and behavior patterns as the
season progresses. Use reference books from the library or garden
center to identify pests. If you can't find an accurate description
there, consult someone in your local extension office. Learn about the
insect's life cycle, behavior, and natural enemies.
Plant diseases may be caused by pathogens including fungi,
nematodes, bacteria, or viruses. Each pathogen is capable of infecting
only certain plants. Infection occurs under particular environmental
conditions, with symptoms of the disease appearing later. To identify
plant diseases accurately, compare visible signs and symptoms of the
disease with descriptions in reference books. Some diseases are more
difficult to identify, and you may need a laboratory analysis or the
help of an expert. These services are available through landscape
professionals or your local extension office.

Determine if a Control Measure is needed

Determine if the damage is severe enough to justify a management
tactic. Is the damage actually affecting the health of the plant? If not,
does it make the plant look bad enough to detract from the
appearance of your landscape? You may become alarmed if you
notice that caterpillars are making holes in leaves, but if the damage
is slight or occurs late in the season, you probably won't need to
control the caterpillars.
Are the pest's natural enemies present? In most cases, they will be. If
so, an application of a nonselective insecticide could kill them,
allowing the pest population to rebound uninhibited by predators and
parasites, which may have been providing significant control.
Choose a Method
If a control is needed, consider physical or bio rational methods first.
If they are unavailable or impractical, you may need to carefully use
a conventional chemical control.
Physical methods
Pests can be removed from plants physically. For example, some
aphids and mites can be knocked off by spraying the plant with
water. Bagworm larvae can be picked off an infested plant.
You can use traps to catch certain pests, and barriers to protect plants
from insect attack or disease infection. One effective method for
controlling gypsy moth larvae on small numbers of trees is to put a
band of folded burlap around the tree trunk to provide an artificial
resting site for the caterpillars, and then destroy the caterpillars that
gather there. Applying an anti-transpiring spray to lilac leaves in
summer to prevent infection by the spores of powdery mildew is
another example of a protective barrier.
In some cases, the best solution may be physically removing the plant
and replacing it with one that will not be affected by the pest or
disease. Thinning crowded plants to improve air circulation can
reduce many disease problems.
Bio rational methods
Bio rational methods can be divided into two groups. The first group
includes living organisms that can kill the pest. The second group
includes naturally occurring bio chemical’s that are harmful to the
pest yet often are harmless to other living organisms.
Insect pests frequently have natural enemies that are beneficial to the
landscape. These beneficial insects often exist in the landscape
naturally, but they also can be introduced. "Beneficial’s" may be
predators or parasites. One common example of a beneficial predator
is the lady beetle. Both the larvae and adult lady beetles eat aphids
and other soft-bodied insects. Other predators include lacewings,
spined soldier bugs, flower flies, and spiders. Parasites live on and
often kill another organism, called the host. Some parasitic wasps use
caterpillars, whiteflies, aphids, and soft scales as hosts.An example
of a method that uses a naturally occurring biochemical is the
bacterium Bacillus thuringiensis. Bacillus thuringiensis contains a
protein that is poisonous to specific insects, yet harmless to other
organisms. Bt can be sprayed on plants. When the sensitive insect
pest feeds on the sprayed leaves, it will ingest the protein and be
killed.

2.3 Bio pesticides/Bio insecticides

Bio pesticides are certain types of pesticides derived from such natural
materials as animals, plants, bacteria, and certain minerals. For example,
canola oil and baking soda have pesticidal applications and are
considered bio pesticides.
Classification of Bio pesticide
Bio pesticides fall into three major classes-
1. Biochemical pesticides are naturally occurring substances that control
pests by non-toxic mechanisms. Conventional pesticides, by contrast, are
generally synthetic materials that directly kill or inactivate the pest.
Biochemical pesticides include substances that interfere with mating,
such as insect sex pheromones, as well as various scented plant extracts
that attract insect pests to traps. Because it is sometimes difficult to
determine whether a substance meets the criteria for classification as a
biochemical pesticide, EPA has established a special committee to make
such decisions.
2. Microbial pesticides consist of a microorganism (e.g., a bacterium,
fungus, virus or protozoan) as the active ingredient. Microbial pesticides
can control many different kinds of pests, although each separate active
ingredient is relatively specific for its target pest. For example, there are
fungi that control certain weeds and other fungi that kill specific insects.
The most widely used microbial pesticides are subspecies and strains of
Bacillus thuringiensis, or Bacillus thuringiensis. Each strain of this
bacterium produces a different mix of proteins and specifically kills one
or a few related species of insect larvae. While some Bacillus
thuringiensis ingredients control moth larvae found on plants, other
Bacillus thuringiensis ingredients are specific for larvae of flies and
mosquitoes. The target insect species are determined by whether the
particular Bacillus thuringiensis produces a protein that can bind to a
larval gut receptor, thereby causing the insect larvae to starve.
3. Plant-Incorporated-Protestants (PIPs) are pesticidal substances that
plants produce from genetic material that has been added to the plant.
For example, scientists can take the gene for the Bacillus thuringiensis
pesticidal protein and introduce the gene into the plant's own genetic
material. Then the plant, instead of the Bacillus thuringiensis bacterium,
manufactures the substance that destroys the pest. The protein and its
genetic material, but not the plant itself, are regulated by EPA.
Advantages of bio pesticides
• Bio pesticides are usually inherently less toxic than conventional
pesticides.
• Bio pesticides generally affect only the target pest and closely related
organisms, in contrast to broad spectrum, conventional pesticides that
may affect organisms as different as birds, insects and mammals.
• Bio pesticides often are effective in very small quantities and often
decompose quickly, resulting in lower exposures and largely avoiding
the pollution problems caused by conventional pesticides.
• When used as a component of Integrated Pest Management (IPM)
programs, bio pesticides can greatly reduce the use of conventional
pesticides, while crop yields remain high.
Bio-insecticides

Bio-insecticides are organic formulations recommended for the

management of insects that feed on crops. They are different from
chemical pesticides in several ways. They contain live bacteria that
produce toxins which cause stomach poison in the insects and kill them.
 [SCHEDULE T]
[See Rule 157]
GOOD MANUFACTURING PRACTICES FOR AYURVEDIC, SIDDHA AND UNANI
MEDICINES
The Good Manufacturing Practices (GMP) are prescribed as follows in Part I and Part II to
ensure that:
(i) Raw materials used in the manufacture of drugs are authentic, of prescribed quality
and are free from contamination.
(ii) The manufacturing process is as has been prescribed to maintain the standards.
(iii) Adequate quality control measures are adopted.
(iv) The manufactured drug which is released for sale is of acceptable quality.
(v) To achieve the objectives listed above, each licensee shall evolve methodology and
procedures for following the prescribed process of manufacture of drugs which
should be documented as a manual and kept for reference and inspection.
However, under IMCC Act 1970 registered Vaidyas, Siddhas and Hakeems who
prepare medicines on their own to dispense to their patients and not selling such
drugs in the market are exempted from the purview of G.M.P.
PART-I
GOOD MANUFACTRING PRACTICES
Factory Premises:
The manufacturing plant should have adequate space for:-
(i) Receiving and storing raw material
(ii) Manufacturing process areas
(iii) Quality control section
(iv) Finished goods store
(v) Office
(vi) Rejected goods/drugs store
1.2 General Requirements:
1.1(A) Location and surroundings- The factory building for manufacture of Ayurveda,
Siddha and Unani medicines shall be so situated and shall have such
construction as to avoid contamination from open sewerage, drain, public lavatory
or any factory which produces disagreeable or obnoxious odour or fumes or
excessive soot, dust or smoke.
1.1(B) Buildings- The building used for factory shall be such as to permit production of
drugs under hygienic conditions and should be free from cobwebs and
insects/rodents. It should have adequate provision of light and ventilation. The
floor and the walls should not be damp or moist. The premises used for
manufacturing, processing, packaging and labeling will be in conformity with the
provisions of the Factory Act. It shall be located so as to be:
(i) Compatible with other manufacturing operations that may be carried out in
the same or adjacent premises.
(ii) Adequately provided with working space to allow orderly and logical
placement of equipment and materials to avoid the risk of mix-up between
different drugs or components thereof and control the possibility of cross-
contamination by other drugs or substances and avoid the risk of omission of
any manufacturing or control step.
(iii) Designed, constructed and maintained to prevent entry of insects and
rodents. Interior surface (walls, floors and ceilings) shall be smooth and free
from cracks and permit easy cleaning and disinfection. The walls of the room
 in which the manufacturing operations are carried out shall be impervious to
and be capable of being kept clean. The flooring shall be smooth and even
and shall be such as not to permit retention or accumulation of dust or waste
products.
(iv) Provided with proper drainage system in the processing area. The sanitary
fittings and electrical fixtures in the manufacturing area shall be proper and
safe.
(v) Furnace/Bhatti section could be covered with tin roof and proper ventilation,
but sufficient care should be taken to prevent flies and dust.
(vi) There should be fire safety measures and proper exits should be there.
(vii) Drying space- There should be separate space for drying of raw material, in
process medicine or medicines which require drying before packing. This
space will be protected from flies/insects/dusts, etc., by proper flooring,
wiremash windows, glass pances or other material.
Water Supply- The water used in manufacture shall be pure and of potable
1.1(C)
quality. Adequate provision of water for washing the premises shall be made.
Disposal of Waste- From the manufacturing sections and laboratories the waste
1.1(D)
water and the residues which might be prejudicial to the workers or public health
shall be disposed off after suitable treatment as per guidelines of pollution control
authorities to render them harmless.
Containers’ Cleaning- In factories where operations involving the use of
1.1(E)
containers such as glass bottles, vials and jars are conducted, there shall be
adequate arrangement separated from the manufacturing operations for washing,
cleaning and drying of such containers.
Stores- Storage should have proper ventilation and shall be free from dampness.
1.1(F)
It should provide independent adequate space for storage of different types of
material, such as raw material, packaging material and finished products.
Raw Materials- All raw materials procured for manufacturing will be stored in the
1.1(F)(A)
raw materials store. The manufacture based on the experience and the
characteristics of theparticular raw material used in Ayurveda, Siddha and Unani
system shall decide the use of appropriate containers which would protect the
quality of the raw material as well as prevent it from damage due to dampness,
microbiological contamination or rodent and insect infestation, etc. If certain raw
materials require such controlled environmental conditions, the raw materials
stores may be sub-divided with proper enclosures to provide such conditions by
suitable cabinization. While designing such containers, cabins or areas in the raw
materials store, care may be taken to handle the following different categories of
raw materials:-
(1) Raw material of metallic origin.
(2) Raw material of mineral origin.
(3) Raw material from animal source.
(4) Fresh Herbs.
(5) Dry Herbs or plant parts.
(6) Excipients, etc.
(7) Volatile oils/perfumes & flavours.
(8) Plant concentrates/extracts and exudates/resins.
Each container used for raw material storage shall be properly identified with the
label which indicates name of the raw material, source of supply and will also
clearly state the status of raw material such as ‘UNDER TEST’ or ‘APPROVED’ or
‘REJECTED’. The labels shall further indicate the identity of the particular supply
in the form of Batch No. or Lot. No. and the date of receipt of consignment.
All the raw materials shall be sampled and got tested either by the in-house
Ayurvedic, Siddha and Unani experts (Quality control technical person) or by the
 laboratories approved by Government and shall be used only on approval after
verifying. The rejected raw material should be removed from other raw materials
store and should be kept in a separate room. Procedure of ‘First in first out’
should be adopted for raw materials wherever necessary. Records of the receipt,
testing and approval or rejection and use of raw material shall be maintained.
1.1(F)(B) Packaging Materials- All packaging materials such as bottles, jars, capsules,
etc. shall be stored properly. All containers and closures shall be adequately
cleaned and dried before packing the products.
1.1(F)(C) Finished Goods Stores- The finished goods transferred from the production
area after proper packaging shall be stored in the finished goods stores within an
area marked “Quarantine”. After the quality control laboratory and the experts
have checked the correctness of finished goods with reference to its
packing/labelling as well as the finished product quality as prescribed,, then it will
be moved to ‘Approved Finished Goods Stock” area. Only approved finished
goods shall be dispatched as per marketing requirements. Distribution records
shall be maintained as required.
If any Ayurvedic, Siddha and Unani drug needs special storage conditions,
finished goods store shall provide necessary environmental requirements.
1.1(G) Working Space- The manufacturing area shall provide adequate space
(manufacture and quality control) for orderly placement of equipment and material
used in any of the operations for which these are employed so as to facilitate
easy and safe working and to minimize or to eliminate any risk of mix-up between
different drugs, raw materials and to prevent the possibility of cross-contamination
of one drug by another drug that is manufactured, stored or handled in the same
premises.
1.1(H) Health, Clothing, Sanitation and Hygiene of Workers- All workers employed in
the Factory shall be free from contagious diseases. The clothing of the workers
shall consist of proper uniform suitable to the nature of work and the climate and
shall be clean. The uniform shall also include cloth or synthetic covering for
hands, feet and head wherever required. Adequate facilities for personal
cleanliness such as clean towels, soap and scrubbing brushes shall be provided.
Separate provision shall be made for lavatories to be used by men and women,
and such lavatories shall be located at places separated from the processing
rooms. Workers will also be provided facilities for changing their clothes and to
keep their personal belongings.
1.1(I) Medical Services- The manufacturer shall also provide:-
(a) Adequate facilities for first aid;
(b) Medical examination of workers at the time of employment and periodical
check up thereafter by a physician once a year, with particular attention
being devoted to freedom from infections. Records thereof shall be
maintained.
1.1(J) Machinery and Equipments- For carrying out manufacturing depending on the
size of operation and the nature of product manufactured, suitable equipment
either manually operated or operated semi-automatically (electrical or team
based) or fully automatic machinery shall be made available. These may include
machines for use in the process of manufacture such as crushing, grinding,
powdering, boiling, mashing, burning, roasting,filtering, drying, filling, labeling and
packing, etc. To ensure ease in movement of workers and orderliness in
operations a suitably adequate space will be ensured between two machines or
rows of machines. These machinery and equipments and machinery
recommended is indicated in Part II-A. Proper standard operational procedures
(SOPs) for cleaning maintaining and performance of every machine should be
laid down.
1.1(K) Batch Manufacturing Records- The licensee shall maintain batch manufacturing
record of each batch of Ayurvedic, Siddha and Unani drugs manufactured
irrespective of the type of product manufactured (classical preparation or patent
and proprietary medicines). Manufacturing records are required to provide and
account of the list of raw materials and their quantities obtained from the store,
tests conducted during the various stages of manufacture like taste, colour,
physical characteristics and chemical tests as may be necessary or indicated in
the approved books of Ayurveda, Siddha and Unani mentioned in the First
Schedule of the Drugs and Cosmetics Act, 1940 (23 of 1940). These tests my
include any in-house or pharmacopoeial test adopted by the manufacturer in the
raw material or in the process material and in the finished product. These records
shall be duly signed by Production and Quality Control Personnel respectively.
Details of transfer of manufactured drug to the finished products store including
dates and quantity of drugs transferred along with record of testing of the finished
product, if any, and packaging, records shall be maintained. Only after the
manufactured drugs have been verified and accepted quality shall be allowed to
be cleared for sale.
It should be essential to maintain the record of date, manpower, machine and
equipments used and to keep in process record of various shodhana, bhavana,
buring in fire and specific grindings in terms of internal use.
1.1(L) Distribution Records- Records of sale and distribution of each batch of
Ayurveda, Siddha and Unani Drugs shall be maintained in order to facilitate
prompt and complete recall of the batch, if necessary.
The duration of record keeping should be the date of expiry of the batch, Certain
categories of Ayurvedic, Siddha and Unani medicines like Bhasma, Rasa, Kupi-
pakva, Parpati, Sindura, Karpu/Uppu/Puram, Kushta, Asava-arista, etc. do not
have expiry date, in contrast their efficacy increases with the passage of time.
Hence, records need to be maintained up to 5 years of the exhausting of stock.
1.1(M) Record of Market Complaints- Manufacturers shall maintain a register to record
all reports of market complaints received regarding the products sold in the
market. The manufacturer shall enter all data received on such market
complaints, investigations carried out by the manufacturers regarding the
complaint as well as any corrective action initiated to prevent recurrence of such
market complaints shall also be recorded. Once in a period of six months the
manufacturer shall submit the record such complaints to the Licensing Authority.
The Register shall also be available for inspection during any inspection of the
premises.
Reports of any adverse reaction resulting from the use of Ayurvedic, Siddha and
Unani drugs shall also be maintained in a separate register by each
manufacturer. The manufacturer shall investigate any of the adverse reaction to
find if the same is due to any defect in the product, and whether such reactions
are already reported in the literature or it is a new observation.
1.1(N) Quality Control- Every licensee is required to provide facility for quality control
section in his own premises or through Government-approved testing laboratory.
The test shall be as per the Ayurveda, Siddha and Unani pharmacopoeial
standard. Where the tests are not available, the test should be performed
according to the manufacturer’s specification or other information available. The
quality control section shall verify all the raw materials, monitor in process, quality
checks and control the quality of finished product being released to finished
goods store/warehouse. Preferably for such quality control there will be a
separate expert. The quality control section shall have the following facilities:
(1) There should be 150 sq feet area for quality control section.
(2) For identification of raw drugs, reference books and reference samples
 should be maintained.
(3) Manufacturing record should be maintained for the various processes.
(4) To verify the finished products, controlled samples of finished products of
each batch will be kept till the expiry date of product.
(5) To supervise and monitor adequacy of conditions under which raw materials,
semi-finished products and finished products are stored.
(6) Keep record in establishing shelf life and storage requirements for the drugs.
(7) Manufacturers who are manufacturing patent proprietary Ayurveda, Siddha
and Unani medicines shall provide their own specification and control
references in respect of such formulated drugs.
(8) The record of specific method and procedure of preparation, that is,
“Bhavana”, “Mardana” and “Puta” and the record of every process carried
out by the manufacturer shall be maintained.
(9) The standards for identity, purity and strength as given in respective
pharmacopoeias of Ayurveda, Siddha and Unani systems of medicines
published by Government of India Shall be complied with.
(10) All raw materials will be monitored for fungal, bacterial contamination with a
view to minimize such contamination.
(11) Quality control section will have a minimum of-
(i) One person with Ayurveda/Unani/Siddha qualification recognized under
Schedule II of Indian Medicine Central Council Act, 1970. Two other
persons, one each with Bachelor qualification in
Botany/Chemistry/Pharmacy could be on part-time or on contractual basis.
(ii) The manufacturing unit shall have a quality control section as explained
under Section 35(ii). Alternatively, these quality control provisions will be met
by getting testing, etc., from a recognized laboratory for Ayurveda, Siddha
and Unani drugs; under Rule 160-A of the Drugs and Cosmetics Act. The
manufacturing company will maintain all the record of various tests got done
from outside recognized laboratory.
(iii) List of equipment recommended is indicated in Part II-C.
1.2 Requirement for Sterile Product:
(A) Manufacturing Areas– For the manufacture of sterile Ayurvedic, Unani and
Siddha drugs, separate enclosed areas specifically designed for the purpose shall
be provided. These areas shall be provided with air locks for entry and shall be
essentially dust free and ventilated with an air supply. For all areas where aseptic
manufacture has to be carried out, air supply shall be filtered through bacteria
retaining filters (HEPA Filters) and shall be at a pressure higher than in the
adjacent areas. The filters shall be checked for performance on installation and
periodically thereafter the record of checks shall be maintained. All the surfaces in
sterile manufacturing areas shall be designed to facilitate cleaning and
disinfection. For sterile manufacturing routine microbial counts of all Ayurvedic,
Siddha and Unani drug manufacturing areas shall be carried out during
operations. Results of such count shall be checked against established in-house
standards and record maintained.
Access to manufacturing areas shall be restricted to minimum number of
authorized personnel. Special procedure to be followed for entering and leaving
the manufacturing areas shall be written down and displayed.
For the manufacturing of Ayurvedic, Siddha and Unani drug that can be sterilized
in their final containers, the design of the areas shall preclude the possibility of the
products intended for sterilization being mixed with or taken to be products
already sterilized. In case of terminally sterilized products, the design of the areas
shall preclude the possibility of mix-up between non-sterile products.
(B) Precautions against contamination and mix:
 (a) Carrying out manufacturing operations in a separate block of adequately
isolated building or operating in an isolated enclosure within the building,
(b) Using appropriate pressure differential in the process area.
(c) Providing a suitable exhaust system.
(d) Designing laminar flow sterile air system for sterile products.
(e) The germicidal efficiency of UV lamps shall be checked and recorded
indicating the burning hours or checked using intensity.
(f) Individual containers of liquids and ophthalmic solutions shall be examined
against black-white background fitted with diffused light after filling to ensure
freedom from contamination with foreign suspended matter.
(g) Expert technical staff approved by the Licensing Authority shall check and
compare actual yield against theoretical yield before final distribution of the
batch.
All process controls as required under master formula including room
temperature, relative humidity, volume filled, leakage and clarity shall be
checked and recorded.
PART-II
A. LIST OF RECOMMENDED MACHINERY, EQUIPMENT AND MINIMUM
MANUFACTURING PREMISES REQUIRED FOR THE MANUFACTURE OF
VARIOUS CATEGORIES OF AYURVEDIC, SIDDHA SYSTEM OF MEDICINES
One machine indicated for one category of medicine could be used for the manufacturing of
other category of medicine also. Similarly some of the manufacturing areas like powdering,
furnace, packing of liquids and Avaleha, Paks, could also be shared for these items.

Sl.No. Category of Medicine Minimum Machinery/equipment

manufacturing recommended
space required
(1) (2) (3) (4)
1200 Square feet
covered area with
separate cabins or
partitions for each
activity. If Unani
medicines are
manufactured in
same premises an
additional area of
400 sq. feet will be
required.
1. Anjana/Pisti 100 sq. feet. Karel/mechanized/motorized, karel.
End runner/Ball-Mill Sieves/Shifter.
2. Churna / Nasya/ 200 sq feet Grinder/disintegrator/Pulveriser/
Manjan/Lepa/ Powder mixer/sieves/shifter.
Kwath Churn
3. Pills/Vati /Gutika 100 sq. feet Ball Mill, Mass mixer/powder mixer,
Matirai and tablets Granulator, drier, tablet compressing
machine, pill/vati cutting machine,
stainless steel trays/container for
storage and sugar coating, polishing
pan in case of sugar-coated
tablets,mechanised chattoo (for
mixing guggulu) where required.
Sl.No. Category of Medicine Minimum Machinery/equipment
manufacturing recommended
space required
(1) (2) (3) (4)
4. Kupi pakava/Ksara/ 150 sq. feet Bhatti, Karahi/Stainless steel
Parpati/LavanaBhasma Vessels/Patila Flask, Multani
Satva/Sindura Karpu/ Matti/Plaster of Paris, Copper Rod,
Uppu / Param Earthern container, Gaj Put Bhatti,
Mufflefurnace(Electrically operated)
End/EdgeRunner, Exhaust Fan,
Wooden/S.S.Spatula.
5. Kajal 100 sq. feet Earthern lamps for collection of Kajal,
Triple Roller Mill, End Runner,
Sieves, S.S.Patila, Filling/ packing
and manufacturing room should be
provided with exhaust fan and ultra
violet lamps.
6. Capsules 100 sq. feet Air Conditioner, De-humidifier,
hygrometer, thermometer, Capsule
filling machine and chemical balance.
7. Ointment/Marham Pasai 100sq. feet Tube filling machine, Crimping
Machine/Ointment Mixer, End
Runner/ Mill (Where required) S.S.
Storage Container S.S.Patila.
8. Pak/Avaleh/Khand/ 100 sq. feet Bhatti section fitted with exhaust fan
Modak/Lakayam and should be fly proof, Iron
Kadahi/S.S. Patila and S.S. Storage
container.
9. Panak, Syrup / Pravahi 150 sq, feet Tincture press, exhaust fan fitted and
Kwath Manapaku fly proof, Bhatti section, Bottle
washing machine, filter press /
Gravity filter, liquid filling machine,
P.P. Capping Machine.
10. Asava / Arishta 200 sq. ft Same as mentioned above.
Fermentation tanks, containers and
distillation plant where necessary,
Filter Press.
11. Sura 100 sq. ft Same as mentioned above plus
Distillation plant and Transfer pump.
12. Ark Tinir 100 sq. ft Maceration tank, Distillation plant,
Liquid filling tank with tap / Gravity
filter/Filter press, Visual inspection
box.
13. Tail/Ghrit Ney 100 sq. ft Bhatti, Kadahi/S.S. Patila
S.S.Storage Containers, Filtration
equipment, filling tank with tap/Liquid
filling machine.
14. Aschyotan / Netra Malham 100 sq. ft Hot air oven electrically heated with
Panir/Karn Bindu/Nasa- thermostatic control, kettle gas or
bindu electrically heated with suitable
mixing arrangements, collation mill,
or ointment mill, tube filling
Sl.No. Category of Medicine Minimum Machinery/equipment
manufacturing recommended
space required
(1) (2) (3) (4)
equipment, mixing and storage tanks
of stainless steel or of other suitable
material sintered glass funnel, seitz
filter or filter candle, liquid filling
equipment, autoclave.
15. Each manufacturing unit 200 sq. ft
will have a separate area
for Bhatti, furnace boilers,
puta, etc. This will have
proper ventilation, removal
of smoke, prevention of
flies, insets, dust etc. The
furnace section could have
tin roof.

B. LIST OF MACHINERY, EQUIPMENT AND MINIMUM MANUFACTURING PREMISES

REQUIRED FOR THE MANUFACTURE OF VARIOUS CATEGORIES OF UNANI
SYSTEM OF MEDICINES
One machine indicated for one category of medicine could be used for the manufacturing of
other category of medicine also. Similarly some of the manufacturing areas like powdering,
furnace, packing of liquids could also be shared for these items.

Sl.No. Category of Minimum manufacturing Machinery/equipment

Medicine space required recommended
(1) (2) (3) (4)
1200 square feet covered
area with separate cabins,
partitions for each activity.
If Ayurveda / Siddha
Medicines are also
manufactured in same
premises an additional
area of 400 square feet
will be required.
1. Itrifal Tirya/majoon/ 100 sq. feet Grinder/ Pulveriser, Sieves, powder
Laooq/Jawarish mixer (if required), S.S. Patilas, Bhatti
Khamiras and other accessories, plant mixer for
Khamiras.
2. Arq. 100 sq. feet Distillation Plant (garembic) S.S.
storage tank, Boiling Vessel, Gravity
filter, Bottle filling machine, Bottle
washing machine, Bottle drier.
3. Habb (Pills) and 100 sq. feet Ball Mill, Mass Mixer/Powder mixer,
tablets. Granulator drier, tablet compressing
machine, pill/vati cutting machine,
stainless steal trays/ container for
storage and sugar coating, polishing
Sl.No. Category of Minimum manufacturing Machinery/equipment
Medicine space required recommended
(1) (2) (3) (4)
pan in case of sugar-coated tablets,
mechanized chattoo, (for mixing
guggul) where required.
4. Sufoof (Powder) 200 sq. feet Grinder / pulveriser, Sieves, Trays,
Scoops, Powder mixer (where
required).
5. Raughan (oils) 100 sq. feet Oil Expeller, S.S. Patilas Oil filter
(Crushing and bottle, Filling machine, Bottle drier,
boiling) Bhatti.
6. Shiyaf, Surma, 100 sq. feet End runner, mixing S.S. Vessel.
Kajal
7. Marham, Zimad 100 sq. feet Kharal, Bhatti, End runner, Grinder,
(Ointment) Pulveriser, Triple Roller Mill (if
required).
8. Qurs (Tab.) 100 sq. feet Grinder/Pulveriser, Sieves, Powder
mixer (where needed), Granulator,
Drier, Tablet Compressing Machine,
Die punches Trays, O.T. Apparatus,
Balance with weights, Scoops, Sugar
Coating Pan, polishing pan, Heater.
9. Kushta 100 sq. feet Bhatti, Kharal, Sil Batta, Earthen pots.
10. Murabba 100 sq. feet Aluminium Vessels 50-100 kgs.
Capacity, Gendna, Bhatti.
11. Capsule 100 sq. feet Pulveriser, Powder mixer (where
needed), capsule filling machine, Air
conditioner, De-humidifier, Balance
with weights, storage containers,
glass.
12. Sharbat and 100 sq. feet Tinctum Press, exhaust fan fitted,
Joshanda Bhatti section, Bottle washing
machine, Filter Press Gravity filter,
Liquid filling tank with tap/liquid filling
machine, hot air oven electrically
heated with thermostatic control,
kettle.
13. Qutoor-e- Chashm 100 sq. feet Hot air oven electrically heated with
and Marham (Eye thermostatic control, kettle.
drops, eye
ointment)

C. LIST OF EQUIPMENT RECOMMENDED FOR IN-HOUSE QUALITY CONTROL

SECTION
(Alternatively, unit can get testing done from the Government approved laboratory).

(A) CHEMISTRY SECTION (B) PHARMACOGNOSY SECTION

1. Alcohol Determination Apparatus (complete 1. Microscope Binoculor.
set)
(A) CHEMISTRY SECTION (B) PHARMACOGNOSY SECTION
2. Volatile Oil Determination Apparatus. 2. Dissecting Microscope.
3. Boiling Point Determination Apparatus. 3. Microtome.
4. Melting Point Determination Apparatus. 4. Physical Balance.
5. Refractometer. 5. Aluminium Slide Trays.
6. Polarimeter. 6. Stage Micrometer.
7. Viscometer. 7. Camera Lucida (Prism and Mirror
Type).
8. Tablet Disintegration Apparatus. 8. Chemicals, Glassware etc.
9. Moisture Meter.
10. Muffle Furnace.
11. Electronic Balance.
12. Magnetic Stirrer.
13. Hot Air Oven.
14. Refrigerator.
15. Glass/Steel Distillation Apparatus.
16. LPG Gas Cylinders with Burners.
17. Water Bath (Temperature controlled.)
18. Heating Mantles/ Hot Plates.
19. TLC Apparatus with all accessories (Manual)
20. Paper Chromatography apparatus with
accessories.
21. Sieve size 10 to120 with Sieve shaker.
22. Centrifuge Machine.
23. Dehumidifier.
24. pH Meter.
25. Limit Test Apparatus.

Note: - The above requirements of machinery, equipments, space are made subject to the
modification at the discretion of the Licensing Authority; if he is of the opinion that having
regard to the nature and extent of the manufacturing operations it is necessary to relax or
alter them in the circumstances in a particular case.
By.Santosh Bhadkariya

UNIT-III
Topic-2
HERBAL EXCIPIENTS
Herbal Excipients
The Herbal or natural excipients have a great advantage over their synthetic analogues as these
are non-toxic, less expensive and freely available. The increasing awareness about these herbal
excipients, which are manly polymers of natural origin, the pharmaceutical industries is getting
more inclined towards their use in formulation development. The plant derived gums, mucilage’s
from natural sources like carrageenan, thaumatin, lard, storax, agar, gum acacia, tragacanth and
many more to name comply with many requirements of pharmaceutical excipients. These can be
preferred for formulation development as being stable and involving less regulatory issues as
compared to their synthetic counter parts. They can also be easily modified to meet the specific
needs, thereby being a potent and economic vehicle for delivering active pharmaceutical
ingredient in formulation. Thus present study aims to throw light on the potential of natural
excipients which can be proposed to be used as diluent, binder, Disintegrants as well as lubricant
in various types of formulations as they are biocompatible and capable of giving additional
nutrition to the developed dosage form.

Excipients are defined as ‘the substance used as a medium for giving a medicament. The specific
application of natural polysaccharide polymers in pharmaceutical formulations include to aid in
the processing of the drug delivery system during its manufacture, protect, support or enhance
stability, bioavailability or patient acceptability, assist in product identification, or enhance any
other attribute of the overall safety, effectiveness or delivery of the drug during storage or use .
Several pharmaceutical excipients of plant origin, like starch, agar, alginates, carrageen an, guar
gum, xanthan gum, gelatin, pectin, acacia, tragacanth, and cellulose find applications in the
pharmaceutical industry as binding agents, disintegrates, sustaining agents, protective’s, colloids,
thickening agents, gelling agents, bases in suppositories, stabilizers, and coating materials. As
plants sources are renewable and can be cultivated or harvested in sustainable manner, can
supply constant availability of raw material. Waste from food industry can be achieved as a raw
material to extract herbal excipients. These are other reasons for increase in demand of herbal
material as excipients. However, substances from plant origin also pose several potential
challenges such as being synthesized in small quantities and in mixtures that are structurally
complex, which may differ according to the location of the plants as well as other variables such
as the season. This may result in a slow and expensive isolation and purification process.
Another issue that has become increasingly.

Pharmaceutical Excipient

Pharmaceutical excipients can be defined as non-active ingredients that are mixed with
therapeutically active compounds to form medicines. The ingredient which is not an active
compound is regarded as an excipients. Excipients affect the behavior and effectivenessof
thedrug product more and more functionality and significantly. The variability of active
compounds, excipients and process are obvious components for the product variability.
Classification of Excipients

Excipients are commonly classifiedaccording totheir application and function in the drug
products-

• Binder and Diluent

• Lubricants,Glidants,Disintegrants
• Polishing film former,Coating Agents
• Plasticizer,Colouring
• Suspending Agent, Preservatives
• Flavourig, Sweeteners, Taste Improving Agent
• Printing Ink, Dispersing Agent Gum

Advantage of Herbal Excipients

1. Biodegradable- Naturally occurring polymer produced by all living organisms. They

show no adverse effects on the environment or human being.
2. Biocompatible and Nontoxic- Chemicallynearly all of these plant materials are
carbohydrates in nature and composed of repeating monosaccharide units. Hence
they are non-toxic.
3. Economic- They are cheaper and their production cost is less than synthetic material.
4. Safe and devoid of side effect-They are from a natural source and hence, safe and
without side effects.
5. Easy availability-In many countries they areproduced due to their application in man.

Disadvantages of Herbal Excipients

1. Microbial contamination– During production, they are exposed to external environment

and hence, there are chances of microbial contamination.
2. Variation– Synthetic manufacturing is controlled procedure with fixed quantities of
ingredients while production of natural polymers is dependent on environment and
various physical factors.
3. The uncontrolled rate of hydration—Due to differences in the collection of
natural materials at different times, as well as differences in region, species, and
climate conditions the percentage of chemical constituents present in a given
material may vary.
4. Slow Process– As the production rate is depends upon the environment and many
other factors, it can’t be changed. So natural polymers have a slow rate of production.
5. Heavy metal contamination– There are chances of Heavy metal contamination
often associated with herbal excipients.
7.2 Significance of substances of natural origin as excipients
Pharmaceutical excipients can be defined as non-active ingredients that are mixed with
therapeutically active compounds to form medicines. The ingredient which is not an active
compound is regarded as an excipient. - Excipients affect the behavior and effectiveness of the
drug product more and more functionality and significantly. The variability of active compounds,
excipients and process are obvious components for the product variability Natural excipients and
derivatives occur ubiquitously throughout the plant and animal kingdoms. Examples of polymers
or derivatives that have been used or investigated as vaccine adjuvants are Individual saponins
derived from the South American tree Quillaja saponaria. Keyhole limpet hemocyanin, a non-
heme copper containing protein found in arthropods. MPL, a monophosphoryl derivative of the
Lipid a molecule found in gram-negative bacteria. Leishmania elongation initiation factors, a
protein produced by the parasite leishmania. Ricin, a potent immunotoxin obtained from the
seeds of castor bean plants.

7.3 Colorants
Colorant/color additiveis a substance that is added or applied in order to change the Colour of a
material or surface. Colorants can be used for many purposes including printing, painting, and
for Colouring many types of materials such as foods and plastics. Colorants work by absorbing
varying amounts of light at different wavelengths (or frequencies) of its spectrum, transmitting
(if translucent) or reflecting the remaining light in straight lines or scattered.

Most colorants can be classified as dyes or pigments, or containing some combination of these.
Typical dyes are formulated as solutions; while pigments are made up of solid particles
suspended and are generally suspended in a vehicle (e.g., linseed oil). The color a colorant
imparts to a substance is mediated by other ingredients it is mixed with such
as binders and fillers are added, for example in paints and inks. In addition, some colorants
impart Colour through reactions with other substances.Colorants, or their constituent compounds
may be classified chemically as inorganic (often from a mineral source) and organic.

In India, there are more than 450 plants that can yield dyes. In addition to their dye-yielding
characteristics, some of these plants also possess medicinal value. The use of natural products
together with their therapeutic properties is as ancient as human civilization and for a long time,
mineral, plant and animal products were the main sources of drugs.

Classification

• Natural dyes obtained from plants - Berry, flower, bark, leaf, seed etc. (e.g. Catechu,
Indigofera, Myrobalan and Pomegranate).

• Natural dyes obtained from insects – Cochineal and lac.

 • Natural dyes obtained from animal – Mollusk, murex snail, cuttlefish and shellfish.

• Natural dyes obtained from mineral – Clay, ochre and malachite.

7.4 Sweeteners
A sugar substitute is a food additive that provides a sweet taste like that of sugar while
containing significantly less food energy than sugar-based sweeteners, making it a zero-
calorie or low-calorie sweetener. Artificial sweeteners may be derived through manufacturing of
plant extracts or processed by chemical synthesis. Sugar alcohols such as erythritol, xylitol,
and sorbitol are derived from sugars. In 2017, sucralose was the most common sugar substitute
used in the manufacture of foods and beverages.

Steviol glycosides are a gaggle of extremely sweet diterpene glycosides contained within the
leaves of stevia. Mogrosides, extracted from monk fruit are a gaggle of cucurbitane-type
triterpenoid glycosides. Glycyrrhizin is an oleanane-type triterpenoid organic compound derived
from the underground elements of Glycyrrhiza plant. Dates are wonderful sweeteners loaded
with K, copper, iron, manganese, metallic element and pyridoxal. The syrup is an excellent
sweetener enriched in manganese, Calcium, Potassium, and Zn.

Stevia

Stevia rebaudiana is a small perennial growing up to 6580 cm tall, with sessile, oppositely
arranged leaves. Different species of Stevia contain several potential sweetening compounds,
with S. rebaudiana being the sweetest of all.

Chemical constituents

Eight ent-kaurene glycosides namely dulcoside A, rebaudiosides A to E, steviolbioside, and

stevioside produce the sweet taste sensation. These glycosides are mainly compounds of the
diterpene derivative steviol.

Pharmacological actions

Stevia is used in many parts of the world as a non-caloric sweetener. Along with sweetness, a
bitter taste is also felt in humans. As an extract, this herb was found to have similar potency with
regard to sweetness as a 10% sucrose solution at either pH 3.0 or 7.0.

Uses of Stevia

• Stevia is safe for diabetics, as it does not affect blood sugar levels.
 • Stevia does not have the neurological or renal side effects as other artificial sweeteners.

• Stevia possess anti-fungal and anti-bacterial properties in addition to its other versatile
uses. It can be safely used in herbal medicines, tonics for diabetic patients and also in
daily usage products such as mouthwashes and toothpastes.

• Mild Stevia leaf tea offers excellent relief for an upset stomach.

7.5 Binders
Binder excipients are formulated to act as an adhesive to literally “bind together” powders,
granules and other dry ingredients to impart to the product the necessary mechanical strength.
They can also give volume to low active dose tablets. Commonly used in wet granulation,
binders are added to create a more effective and predictable granule formation. Binders are
classified according to their application. For example, solution binders are dissolved in a solvent,
such as gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, sucrose and
polyethylene glycol.

Binder’s square measure the agents utilized to impart cohesiveness or adhesion to the granules.
This ensures that the pill remains intact when compressed in addition to the flow qualities by the
formulation of granules of derived hardness and size. The employment of genus Dioscorea
rotundata as a binder and disintegrant in pill formulation and therefore has the compressional
propertiesa. The consequences of columbiform bird pea and plantain starches on the
compressional, mechanical and disintegration properties of Paracetamol tablets are investigated.
Starch 1500 has been tested as a wonderful binder, manufacturing a granulation that was
compressible.

7.6 Diluents
Diluents act as fillers in pharmaceutical tablets to increase weight and improve content
uniformity. Natural diluents include starches, hydrolyzed starches, and partially pre-gelatinized
starches. Common diluents include anhydrous lactose, lactose monohydrate, and sugar alcohols
such as sorbitol, xylitol and mannitol. Diluents provide better tablet properties such as improved
cohesion or to promote flow. Mannitol is one of the costliest diluents, however, it is still often
used due to the sensation it provides when it is used in chewable tablets. Diluents must be non-
toxic, commercially available in acceptable grade, physiologically inert, and physically and
chemically stable by themselves as well as in combination with active pharmaceutical
ingredients (APIs).
7.7 Viscosity builders
Viscosity modifiers are designed to change the thickness or texture of pharmaceutical
ingredients. Viscosity modifiers can include such products as thickeners, texturizers, gelation
agents and stiffening agents. Many viscosity modifiers can be used to convert liquids to gels,
pastes or powders to aid formulators in creating the ideal product for end users. A viscosity
modifier can decrease the thickness of a liquid to improve pour ability and ultimately make it
more palatable.

Various thickeners are found in nature or are derivatives of natural thickeners. These ingredients
are polymers that absorb water to expand and increase viscosity. Polyose derivatives like
hydroxyethylcellulose are often employed in products like shampoo or body washes. Gum is
another example of a naturally derived thickener. Others embrace algarroba bean gum, xanthan
gum, and gelatin. Plants and different gums are employed in sensible applications primarily to
thicken or gel binary compound systems and to regulate water. They will conjointly operate as
adhesives, foam stabilizers and impart different specific properties. These thickeners will be
employed in any formula that contains a high level of water. Typically, they will be inconsistent,
as a result of clear formulas to become cloudy, and feel sticky on skin. Xanthan gum is an
associate example of high relative molecular mass additional cellular saccharide created by the
fermentation of the gram negative bacteria genus campestris.

7.8 Disintegrants
Disintegrants are added to oral solid dosage forms to aid in their de-aggregation. Disintegrants
are formulated to cause a rapid break-up of solids dosage forms when they come into contact
with moisture. Disintegration is typically viewed as the first step in the dissolution
process. Examples of Disintegrants include Crosslinked polymers, including crosslinked
polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose
(croscarmellose sodium), and the modified starch sodium starch glycolate. Some of the natural
disintegrating agents are shown below-

1. Lepidus sativum

Lepidium sativum (family-Cruciferae) known as asaliyo and widely used as herbal medicine and
pharmaceutical excipient as disintegrating agent.

2. Isapghula Husk (Plantago ovata)

The seeds of Plantago ovata were soaked in distilled water for 48 hrs and then boiled for few
minutes for complete release of mucilage into water. Mucilage of Plantago ovata at a
concentration of 2 % is also a good disintegratingagent having the additional advantage of being
natural.

3. Hibiscus rosa sinesis linn.

Mucilage Hibisicus rosa-sinensis linn. Of the Malvaceae family is also known as the shoe flower
plant, China rose, Chinese hibiscus. The plant is available in Indian in large quantities and its
mucilage has been found to act as superdisintegrant. The plant contains cyclopropanoids, methyl
sterculate, methyl-2-hydroxysterculate, 2- hydroxysterculate malvate and β-rosasterol.

7.9 Flavors & perfumes

Since primeval times Flavors and Fragrances has been an element of our life. We have been
making it a part of life. By different means we all utilize perfumery and flavor materials, in our
everyday life. Fragrances have a key part in religious ceremonies as it was considered to possess
strengths to cure and protect from evil. We in our routine life starting from morning till night
make different uses of products for personal care and cleanliness which have perfumes. Even
consumables like confectionary contain some type of perfume or flavors. Most fragrance comes
naturally form many plants. This smell is known as aroma which is a Latin word and those floras
which have this aroma are known as aromatic plants. These aromas are extracted from some
odoriferous material called essential oils. There is no dearth of aromatic plants in India. The
country is famous for its rich endowment with aromatic plant. In fact the Vedic literature one can
find many references of Ayurveda Gandhshastra the science of odor which deals with the
cosmetics and fragrances.

Flavoring materials are received from a number of sources, and mostly from plants such as from
flower, leaf, stem or bark. To be employed in food merchandise, the materials area unit typically
extracted from the material to produce an isolate that is simply the flavor. These Flavourig agents
have good importance within the business of medication, particularly in camouflaging with the
medicines by their indispensable flavors. Thus, they are additionally referred to as “masking
agents” or “bitter blockers”. The principal flavors employed in the dental merchandise area unit
peppermint, spearmint, and wintergreen changed with different essential oils of anise, clove,
caraway, pimento, eucalyptus and citrus fruits, menthol, nutmeg, thyme or cinnamon.
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/319242213

Dosage forms of herbal medicinal products and their stability considerations -

an overview

Article · January 2017

DOI: 10.22159/jcr.2017v4i4.16077

CITATIONS READS

23 19,242

2 authors, including:

Kwabena Ofori-Kwakye
Kwame Nkrumah University Of Science and Technology
74 PUBLICATIONS   846 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Film coating potential of natural polysaccharides View project

Development and evaluation of natural gum based ibuprofen matrix tablets for colonic drug delivery View project

All content following this page was uploaded by Kwabena Ofori-Kwakye on 23 August 2017.

The user has requested enhancement of the downloaded file.

 Journal of Critical Reviews

ISSN- 2394-5125 Vol 4, Issue 4, 2017

Review Article
DOSAGE FORMS OF HERBAL MEDICINAL PRODUCTS AND THEIR STABILITY
CONSIDERATIONS-AN OVERVIEW

DORIS KUMADOH1,2, KWABENA OFORI-KWAKYE2*

1Centre for Plant Medicine Research (CPMR), Mampong-Akuapem, Ghana, 2Department of Pharmaceutics, Faculty of Pharmacy and
Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Email: kokwakye.pharm@knust.edu.gh
Received: 08 Nov 2016 Revised and Accepted: 22 Jul 2017
ABSTRACT
There has been an upsurge in the use of herbal medicinal products across both developing and advanced countries. Finished herbal products are
presented in various dosage forms such as decoctions, herbal powders, alcoholic beverages, capsules, tablets, ointments and creams. The growing
demand for herbal medicinal products across the world has resulted in the large scale manufacture of these products. Large scale production leads
to longer storage periods which could lead to deterioration of products, thereby compromise product quality with adverse consequences on patient
safety. Stability studies on herbal products have become necessary to help determine the shelf-life and enhance product quality at all times during
storage periods and usage. Appropriate guidelines for stability testing of finished herbal products provides manufacturers, regulatory authorities
and research institutions with a harmonized system for stability testing. This paper presents an overview of the various herbal dosage forms
commonly available and their stability considerations. This information will help in the production of safe, stable and efficacious herbal medicinal
products for use.
Keywords: Herbal medicines, Herbal dosage forms, Finished herbal products, Stability testing, Shelf-life, Storage temperature
© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/jcr.2017v4i4.16077

INTRODUCTION Dosage forms of herbal medicinal products

Over the last three decades, there has been a huge increase in use of
herbal products across the world. About 80% of the world’s population,
especially those in developing countries, uses herbal medicines as part of
their primary health care needs [1, 2]. In Ghana, it has been estimated
that 70% of the population use herbal medicinal products either alone or
in combination with allopathic medicines for their health needs [3].
Herbal products may be defined as plants, parts of plants or extracts
from plants that are used in healthcare or in combating the disease. To
avoid confusion with culinary herbs, herbs and plant extracts that have
some association with medical uses (prevention and treatment of
diseases) are referred to as ‘herbal medicinal products’ (HMPs) [4].
Many of the plant species currently being used have been used for
centuries in a limited part of the world but the increase in global travel
and communications has resulted in many of these now being used
worldwide [5]. Herbs and plants can be processed and used in different
ways and forms, and they include the whole herb, teas, syrups, essential
oils, ointments, liniments, capsules, and tablets that contain a ground or
powdered form of a raw herb or its dried extract.
Commonly-available herbal dosage forms include decoctions, herbal
teas, tinctures, glycerites, oxymels, and herbal soaps, herbal tablets,
herbal capsules, herbal creams and ointments. Plants and herb
extracts vary in the solvent used for extraction, temperature, and
extraction time, and include alcoholic extracts, vinegars, hot water
extracts, long-term boiled extract of roots or bark (decoctions), and
cold infusion of plants [6]. The growing demand for herbal medicinal
products has made large scale manufacture of these products a
routine. Large scale production may result in longer storage times
and possible product deterioration. Stability studies are useful in the
determination of product shelf-life and enhancement of product
quality [4]. Stability studies may involve physical or sensory tests,
microbiological tests and chemical or chromatographic/spectral
tests. Determination of the chemical stability of a herbal preparation
is very challenging due to the fact that a plant extract may contain
many different compounds. Additionally, plant enzymes such as
esterases, glycosidases or oxidases plays a prominent role in the
decomposition of secondary plant metabolites [7]. This article
provides an overview of the various herbal dosage forms currently
available and their stability considerations.
Dosage forms are the means by which drug molecules or plant parts
are delivered to sites of action within the body. The routes for which
herbal dosage forms may be administered include oral, rectal,
topical, parenteral, respiratory, nasal, ophthalmic and otic [8].
Categorization of finished herbal products into dosage forms will
help to define specific protocols for quality control and stability
testing. Herbal medicinal products may be defined as finished,
labelled medicinal products that contain as active ingredients aerial
or underground parts of plants, or other plant material, or
combinations thereof, whether in the crude state or as plant
preparations [9, 10]. Herbal medicines may contain excipients in
addition to the active ingredients. Medicines containing plant
materials combined with chemically defined active substances,
including chemically defined, isolated constituents of plants, are not
considered to be herbal medicines [9]. Finished herbal products or
herbal drug preparations are varied and various solvents may be
used for their extraction, distillation, expression, fractionation,
purification, concentration or fermentation. These include
comminuted or powdered herbal drugs, tinctures, extracts, essential
oils, expressed juices and processed exudates [11].
Decoctions
Decoctions are made by boiling the herb in water for a period of time
to extract soluble constituents [12]. The water decoction of a mixture
of 2-12 herbal materials is the commonest traditional herbal dosage
form [13]. Decoctions are normally suitable for hard plant materials
such as barks and roots and may also be prepared from herbs with
sparingly soluble constituents [14]. Decoctions are normally intended
for immediate use, ideally within a 24-hour period, with about a 72-
hour maximum limit if stored in a very cool place [12]. Excipients such
as preservatives may be used in decoctions to prevent spoilage if long
term storage is desired [15]. In this case, the stability of the
preparation should be conducted to determine the shelf-life of the
product at a particular storage condition. Decoctions may be
sweetened using a syrup or honey [16]. Sijunzi decoction, a Chinese
herbal remedy consists of Panax ginseng, Poria cocos, Atractylodes
macrocephala and Glycyrrhiza uralensis. A high-performance liquid
 Kwakye et al.
chromatography tandem mass spectrometry (LC/MSn) analysis of
three active compounds ginsenoside (from P. ginseng) and flavonoid
and triterpenoid (from G. uralensis) in both Sijunzi decoction and the
single herb extracts was conducted. The concentration ratios of major
active components found in the individual herbs were different from
those in the decoction indicating the influence of the decocting process
in the difference in the amount of active components [17]. The
decoction extract of Cassia fistula pod pulp was chemically stable
(rhein content) after 6 mo of storage under accelerated (40 °C±2
°C/75% RH±5% RH and real time storage (30 °C±2 °C/75% RH±5%
RH) conditions. However, the anti dermatophyte activity of the
decoction extract was very low compared with the hydrolysed
mixture [18].
Tinctures
Tinctures are normally alcohol and water extracts of plant materials.
Many plant constituents dissolve more easily in a mixture of alcohol and
water than in pure water [19]. The preparation of tinctures by
maceration of herbal parts in water-ethanol solutions results in the
extraction of many structurally diverse compounds with varying
polarities. The wide chemical diversity of the chemical constituent’s
demands quality control analytical tools optimized for the detection of
single chemical compounds or a specific group of compounds [20]. Both
NMR and MS have been successfully used to obtain a metabolic
fingerprint to distinguish between different commercial tinctures, assess
batch to batch homogeneity and evaluate the product degradation after
the expiry date of the batch. There is the added advantage of the alcohol
in a tincture being a preservative, allowing the extract to be kept for
several years. The alcohol content of the finished extract needs to be at
least 20 %v/v to adequately preserve it. Most commercially produced
tinctures have a minimum alcohol content of 25 % v/v.
An alcohol content of 25 %v/v is recommended for water-soluble
constituents like tannins, mucilage and certain flavonoids and some
saponins, while an alcohol concentration of 45-60 %v/v is required
for alkaloids, essential oils, some glycosides and most saponins, and
90 % v/v alcohol for resins and oleoresins [21]. The use of the right
ethanol concentration is important in maximizing the quality of the
herbal preparations [22]. When kept properly, most tinctures have a
shelf life of around five years [23]. However, the shelf-lives of
Passionflower (60 % v/v) and milk-thistle (60 % v/v) tinctures used
in phytotherapy was found to be 6 mo and 3 mo, respectively, at 25
°C, due to the low thermal stability of the constituents determined
from accelerated and long term testing [24]. Improperly stored
samples of Strong Iodine Tincture which had been subject to
household use for long periods showed an iodine content much
higher than that permitted by the official pharmacopoeia [25]. The
principal change during storage of tinctures of Cannabis sativa L. is
the decarboxylation of Δ9-tetrahydrocannabinolic acid A (THCA) to
Δ9-tetrahydrocannabinol (THC). This occurred after 15 mo storage
in the ‘fridge’ and was comparable to 3 mo storage on the ‘shelf’ [26].
Herbal glycerites
Glycerites are made like tinctures but in this instance, glycerine is
used in the extraction process instead of a mixture of alcohol and
water. A glycerite will keep well as long as the concentration of
glycerine is at least 50 % to 60 % in the finished product. The shelf-
life is only about six months to two years. Glycerine should not be
the solvent of choice for herbs that contain resins and gums; alcohol
is needed to properly extract the active constituents of these herbs.
Glycerites should be refrigerated for best effects [19]. Glycerine is a
good preservative for fresh plant juices, in which half fresh plant
juice and half glycerine are mixed, as it keeps the juice green and in
suspension better than alcohol. This sort of preparation is called a
succus. Glycerine is particularly good in making medicines for
children, and for soothing preparations intended for the throat and
digestive tract, or coughs [23]. Glycerites are normally less potent
than alcoholic extracts and have a shorter shelf life.
Herbal alcoholic beverages (bitters/wines)
Herbal alcoholic beverages are normally ethanolic or hydroethanolic
extracts of herbal materials [27]. Herbal beverages in the form of
spirits and liquors are widely used in Africa, as well as the Southeast
J Crit Rev, Vol 4, Issue 4, 1-8
European and Mediterranean regions as part of the local
gastronomy [28]. They are normally meant for oral use as a
beverage. The herbal material present in the product confers a
certain degree of medicinal effect depending on the type and
quantity used in the preparation [12]. In addition, the presence of
the alcohol in the preparation normally confers a preservative effect
on the product thereby prolonging the shelf-life compared to
decoctions and infusions [29]. The antioxidant, antibacterial and
antifungal activity, as well as the total phenolic and flavonoid
compounds present in an herbal liqueur, were established to be
dependent on storage conditions and duration [30]. The titrable
acidity, pH and percentage alcohol content of pasteurized,
noncarbonated, alcoholic orange juice beverage remained constant
during storage at 4, 25 and 40 ° C for 14 w. However, the
accumulation of furfural and the darkening of the alcoholic beverage
during storage was indicative of the degradation of ascorbic acid in
the product [31].
Oxymels
An oxymel is a specialized sweet and sour herbal honey preparation, a
sweet honey mixed with a little sour vinegar. This combination may be
used as a carrier for herbal infusions, decoctions, concentrates, tinctures,
and other herbal extracts. Oxymels are used as a gargle or as a vehicle for
intense herbal aids such as Garlic, Cayenne, and Lobelia [12]. The
stability of oxymels may depend on the content of honey, vinegar as well
as the preparation for which it is being used as a carrier [19].
Herbal capsules
Capsules are solid dosage forms containing drug and usually,
appropriate filler (s) enclosed in a gelatin container [32]. Capsules
may be available in hard gelatin for dry powdered herbal
ingredients or granules [33], or soft gelatin shells for herbal oils and
for herbal ingredients that are dissolved or suspended in oil. The
gelatin shell readily ruptures and dissolves following oral
administration. Drugs are normally more readily released from
capsules compared to tablets [16]. Capsules may help mask the
unpleasant taste of its contents and uniformity of dosage can be
relatively readily achieved [8]. Herbal capsules normally consist of
hard shelled gelatin capsules with the plant material finely milled
and sifted and filled into shell or extracts of the herbal material(s)
with appropriate excipients such as fillers [34]. The stability of
herbal capsule preparations is relatively better when compared to
aqueous preparations such as decoctions and infusions. Stability and
shelf life of capsule preparations should be determined to provide
appropriate instructions for storage of the product [8]. An
accelerated stability study of herbal capsules indicated for
immunomodulation and stress in India found the change in
quantifiable active components to be within 90% of the initial amount
showing the stability of the product at room temperature for 2 y [35].
Herbal capsules filled with pellets showed a uniform and stable release
of phenolic compounds in various long-term storage conditions,
indicating that the method of preparation of dry herbal extracts affects
the stability of the active ingredients [36]. The carotene content of
most pilot batches of soft gelatin capsules containing thick extracts of
pine needles during long-term (3-24 mo) and accelerated (3-12 mo)
stability studies at 25 °C±2 °C/60%±5% RH and 30 °C±2 °C/65%±5%
RH was found to be satisfactory (≥30 mg%) [37].
Herbal tablets
A tablet is a hard, compressed medication in round, oval or square
shape [32]. The excipients or formulation additives may include:
binders, glidants (flow aids) and lubricants to ensure efficient
tableting; disintegrants to ensure that the tablet breaks up in the
gastrointestinal tract; sweeteners or flavours to mask the taste of bad-
tasting active ingredients; and pigments to make uncoated tablets
visually attractive [8, 16]. A coating may be applied to a tablet to: hide
or mask the taste of the tablet's components; make the tablet
smoother and easier to swallow; protect drug from the acid secretions
of the stomach; and make it more resistant to environmental factors
for stability purposes and extend its shelf life [8, 32].
Herbal tablets are normally designed for oral use with various
herbal materials incorporated for a particular therapeutic effect
2
 Kwakye et al.
using excipients [38]. Like the herbal capsules, incorporation of the
herbal material may be done with the finely powdered and sifted
plant material or extracts from the plant materials using various
solvents which are suitable for oral use [14, 16]. The stability of
herbal tablets should be determined as the shelf life of the tablet is
affected by storage conditions. Herbal tablets containing Rhodiola
rosea L. extract were determined to be stable during six months
storage at 25 °C/60% RH but the tablets failed the stability test at 40
°C/75% RH due to decreased hardness [39].
Herbal ointments
Ointments are semi-solid, greasy preparations for application to the
skin, rectum or nasal mucosa. The base is usually anhydrous
(hydrophobic) and immiscible with skin secretions [32]. Ointments
may be used as emollients or to apply suspended or dissolved
medicaments to the skin [8]. Herbal ointments normally have the
plant material(s) either in finely sifted or extracted form
incorporated into the base [40]. Herbal Ointments should not be
used for deep wounds [19]. Ointments are relatively stable when
compared with other liquid dosage forms [8]. However, the presence
of herbal materials in an herbal ointment may lead to quick
deterioration of the product. The stability of herbal ointments is
necessary to provide appropriate labelling instructions for storage
and shelf-life [41]. The chemical stability of an ointment containing
herbal tinctures of calendula and arnica for the treatment of
haemorrhoids was determined using a stability-indicating thin-layer
chromatography technique. The shelf-life was determined to be one
month and two months at 25 °C±2 °C/60% RH and 5 °C±3 °C, when
protected from light, respectively [41].
Herbal balms
These may be classified as ointments meant for massage into the
skin for relief of body aches and pains. They normally contain herbal
materials which provide a rubefacient effect on the skin and by so
doing cause relief of pain [42]. The stability of herbal balms may be
compared to that of herbal ointments since the bases for
preparation are similar. The difference arises in the type of herbal
material being used to exert a particular effect [16].
Herbal creams
Creams are semi-solid emulsions that are mixtures of oil and water
(hydrophilic) [32]. Herbal creams normally contain the herbal
material in either finely sifted form or incorporated as an extract.
Creams normally contain antimicrobial preservatives due to the
presence of water in the base and may have a relatively shorter shelf
life compared to ointments [40, 42]. Some herbalists tend to confuse
creams and ointments. Herbal creams are those which have a
hydrophilic base. If the base is purely hydrophobic, then the
preparation must be qualified as an ointment [8].
Herbal oils
These are suspensions or solutions of herbal materials in an oily
vehicle. Infused oils are often called macerated oils, and should not
be confused with essential oils, which are aromatic oils isolated by
distilling the plant material [23]. These preparations are normally
meant for external or topical use as liniments [32]. In a few cases,
however, some of these preparations may be meant for oral use
[23]. Herbal materials such as leaves with essential oils may
normally be found incorporated in these oils [43]. The stability
and shelf life of a herbal oil depends largely on the type of oil being
used in the extraction process since the stability of various
essential oils differs [44].
Herbal soaps
A soap is a salt of a fatty acid usually made by saponification of a
fatty acid with caustic soda or a suitable base [45]. Herbal soaps
have the herbal materials incorporated in the detergent base. These
herbal materials normally have an antifungal and antibacterial effect
on the skin and helps in cleansing of the skin [46]. Herbal soaps are
normally meant for microbial skin conditions such as dandruff,
eczema, ringworm and boils [47]. Soaps have a relatively longer
shelf-life when preservatives or antioxidants are added [46].
J Crit Rev, Vol 4, Issue 4, 1-8
Herbal pastes
Pharmaceutically, topical pastes are ointments which may contain as
much as 50 % powder dispersed in a fatty base [32]. These pastes
normally localize the action of irritant or staining materials. They are
normally less greasy than ointments [8]. Herbal pastes may contain
the herbal ingredient dissolved or dispersed in a base (fatty base if it is
meant for topical use or a more aqueous stiff base if it is meant for oral
use as is done in herbal toothpaste) [40]. Herbal oral pastes should
contain only herbal materials that are safe for oral use [48]. The
stability of an herbal paste depends on the type of base used as well as
the nature of the herbal material incorporated [40, 48].
Herbal teas
These are preparations meant for infusion or preparation to be
taken as tea. Prepared infusions should be taken immediately after
preparation since they do not store well due to the use of water in
the extraction process [49]. They normally come as tea bags for hot
infusion [23] or as powdered herbal materials (normally pulverized
leaves) for boiling in hot water for a few minutes before straining
and drinking as tea [50]. The stability of the powdered plant
material used in the preparation depends on the type and nature of
the herbal material as well the moisture content of the powder in the
bags and packaging. The shelf life also depends on the extent the
herbs have been crushed and storage conditions. Teas stored in
airtight containers may last for up to a year whist those stored in tea
bags may last for a shorter period.
Herbal powders
These are preparations that come as powdered herbal materials meant
for direct use or by incorporation into foods, beverages for drinking [23],
insufflations [51], and wounds [52]. They may be finely sifted herbal
materials from various parts of plants meant for a particular therapeutic
effect [50]. Like the herbal teas, the stability of the powder depends on
the type and nature of the herbal material as well as the moisture
content of the powder in the bags and packaging. The dried herb and
extract of the root of Nauclea latifolia S. M., an antimalarial plant found
growing in Africa, was found to be stable under tropical room
temperature conditions for over one year in sealed glass containers [53].
Herbal suppositories
Suppositories are solid dosage forms meant for insertion into the
rectum. They are prepared by moulding with the incorporation of the
medicinal agent into a suitable base which should melt or dissolve at
body temperature to exert the therapeutic effect. Suppositories may be
used for local or systemic effects [8, 32]. Herbal suppositories are
normally prepared by mixing powdered and finely sited herbs or
extracts with cocoa butter as the base [12]. They are normally used to
soothe inflamed surfaces of the nasal mucosa and aid the healing
process; reduce swollen membranes and overcome pus filled discharge
or to act as a laxative to treat constipation [54]. The stability of
suppositories, amongst other factors, depends on the temperature of
storage and packaging. They are relatively stable at low temperatures of
storage. Unless other information on stability is provided from a study, a
shelf life of one month may be appropriate [32].
Herbal pessaries
Pessaries are similar to suppositories but are meant for insertion
into the vagina for local or systemic effects [8, 32]. Herbal pessaries
may also be made using a glycerated-gelatin base which dissolves at
body temperature to release herbal ingredients for the desired local
or systemic effects [55]. The stability of pessaries may be compared
to that of suppositories [32].
Herbal poultices and plasters
Poultices are made by mashing fresh herbs, wrapping in a gauze and
applied to an affected area of the skin after the temperature is
suitable for application [19, 54]. Poultices may be used externally to
relax muscles or to ease minor skin eruptions, poison ivy, insect
bites, superficial wounds, and inflammation. Since they are normally
made from fresh herbs, they should be used immediately and cannot
be stored [16].
3
 Kwakye et al.
Herbal compresses and fomentations
Compresses are normally prepared from an infusion or tincture in
hot or cold water by soaking a cotton cloth or gauze. Compresses
may be used externally and can be either warm or cold. Cold
compresses reduce inflammation and help to relieve pain [12]. They
are usually used in the treatment of sprains, contusions, strains,
inflammation, headaches, and insect bites. Warm compresses are
used to increase circulation to an area and to allow muscles,
tendons, and ligaments to stretch [19].
Herbal liniments
Liniments are for external use for aches and pains. Herbal liniments
are normally used as warming massage mediums to relieve soreness
in muscles and ligaments [16]. Heat-inducing herbs such as cayenne
are normally used in the preparation of liniments together with
alcohol for extraction or a mixture of alcohol and/or oil. Liniments
should not be used on cuts or broken skin [54]. The stability of
liniments is similar to that of herbal oils (if oil was used as a vehicle
in the preparation process).
Herbal baths
These are normally prepared by the addition of fresh or dried herbs
to bath water. An infusion or tincture of an herbal material may also
be added to bath water. Herbs normally used are aromatic in nature
and may contain essential oils that may help in relaxation or stress
relieve [19].
Herbal lozenges
A number of formulations have been developed to pleasantly and
slowly release medicinal properties in the mouth [54]. Lozenges
may be prepared by the use of the powdered herbs together with
excipients such as sugar and honey to provide the sweet taste, gums
(Acacia and tragacanth) and the white of an egg in some instances
[16]. The lozenges normally may be used to sooth soreness in the
throat as well as help in the treatment of throat infections. Lozenges
normally do not contain disintegrating agents. The shelf life of
lozenges may be compared to that of tablets but should be
determined using an appropriate stability protocol [8].
Stability studies of finished herbal products
The World Health Organization (WHO) recommends that stability
data be provided to support the shelf-life proposed for finished
herbal products under the specified conditions of storage [9]. The
shelf-life of a product is the period during which it remains within
acceptable chemical, physical and microbiological stability if stored
correctly [55]. The expiry date is represented on the product to
indicate the end of the shelf life [57]. Finished herbal products are
unique compared to synthetic products due to the varied nature of
constituents that may be present even in an herbal product with only
one herbal ingredient [35]. It is often not feasible to determine the
stability of each active ingredient [58]. The herbal material, in its
entirety, is normally regarded as the active ingredient and a mere
determination of the stability of the constituents with known therapeutic
activity will not usually be sufficient [59]. Constituents (markers) for
stability determination in herbal products may be categorized as;
chemical, analytical and active markers [9, 10]. Chemical markers may
be defined as chemically defined constituents or groups of constituents
of an herbal medicinal product which are of interest for quality control
purposes regardless of whether they possess any therapeutic activity
[10]. The quantity of a chemical marker can be an indicator of the quality
of an herbal medicine. Chemical markers may be used to evaluate
product quality and stability over time and determine the recommended
shelf life [60]. Analytical markers are the constituents or groups of
constituents that serve solely for analytical purposes [57]. Active
markers are the constituents or groups of constituents that contribute to
therapeutic activities [9, 10, 38].
Stability determination of herbal medicinal products
The principle of a stability study is to provide evidence that an active
substance or finished product varies with time under the influence
of a variety of environmental factors such as temperature, humidity
and light. The importance of stability testing is to; evaluate the
J Crit Rev, Vol 4, Issue 4, 1-8
efficacy of a drug; provide background information during the
development phase of the product or drug discovery; develop
suitable packaging information for quality, strength, purity and
integrity of a product during its shelf-life [9, 38, 61].
Mechanisms that may indicate a change in stability include; loss of
activity; change in concentration of active component; alteration in
bioavailability of product; loss of content uniformity; loss of elegance;
formation of toxic degradation products and loss of packaging
integrity. It is difficult to develop analytical methods for herbal
medicines due to the presence of phytochemical constituents which
may be susceptible to enzymatic breakdown of these plant
metabolites. Predictable chemical changes in herbal products includes;
hydrolysis; oxidation (especially in fixed, volatile and essential oils);
racemization; geometric isomerization and poly-merization [61].
General methods for stability testing
The stability of herbal medicinal products may be determined based
on physical and sensory tests, microbial tests and chromatographic/
spectral tests.
Physical and sensory methods
Herbal products, like pharmaceutical products, usually undergo
physical changes during storage. These changes though not usually
quantitative in nature may be used as a guide to check if the
products are deteriorating. These include evaluation of changes in
parameters such as colour, taste, odour, clarity, specific gravity, total
solid residue, viscosity, the moisture content of powders, dissolution
and disintegration tests for capsules and tablets. It must be noted
that some of these methods of assessment such as taste and odour
should be carried out only if they do not affect the safety of the
personnel involved [8, 9, 10, 38].
Microbial tests
Microbial contamination or load tests and preservative efficacy or
challenge tests (where preservatives are used) of finished herbal
products are essential in the determination of stability and shelf life
of the product [62]. Key factors affecting the efficacy of the
antimicrobial preservative added are the active ingredient,
excipients, storage conditions, the container and its closure. The
British Pharmacopoeia states that for a product “it shall be
demonstrated that the antimicrobial activity of the preparation as
such or if necessary, with the addition of a suitable preservative or
preservatives provides adequate protection from adverse effects
that may arise from microbial contamination or proliferation during
storage and use of the preparation” [63]. Analyses of such
parameters with time allows the tracing of stability of the product
and subsequent prediction or estimation of shelf-life. These tests
should be done according to Pharmacopoeia methods (British
Pharmacopoeia, United States Pharmacopoeia, European
Pharmacopeia.), WHO methods, or any other internationally
recognized methods [64]. The microbial tests should involve: Total
viable aerobic plate count; contaminating fungus (yeast and mould);
Salmonella spp.; Escherichia coli and Staphylococcus aureus. Table 1
shows the British Pharmacopoeia acceptance criteria for
microbiological testing of herbal products.
Criteria ‘A’ represents herbal medicinal products containing herbal
drugs, with or without excipients, intended for the preparation of
infusions and decoctions using boiling water (for example herbal
teas, with or without added flavourings).
‘B’ represents herbal medicinal products containing, for example,
extracts and/or herbal drugs, with or without excipients, where the
method of processing (for example, extraction) or, where
appropriate, in the case of herbal drugs, of pre-treatment reduces
the levels of organisms to below those stated for this category).
‘C’ represents herbal medicinal products containing, for example,
extracts and/or herbal drugs, with or without excipients, where it
can be demonstrated that the method of processing (for example,
extraction with low strength ethanol or water that is not boiling or
low-temperature concentration) or, in the case of herbal drugs, of
pre-treatment, would not reduce the level of organisms sufficiently
to reach the criteria required under B.
4
 Kwakye et al.
J Crit Rev, Vol 4, Issue 4, 1-8

Table 1: Acceptance criteria for microbiological tests

Microbiological quality
Total aerobic microbial count
Total yeast and mould count
Bile-tolerant Gram negative
bacteria
Salmonella spp.
Escherichia coli
*British Pharmacopoeia [65]
Acceptance criteria*
A B
Not more than 5x107 CFU per g or
per ml
Not more than 5x105 CFU per g or
per Ml
Not more than 102 CFU per g or
per ml
Absent in 10 g or 10 ml
Absent in 1 g or 1 ml
Not more than 5 x104 CFU per g or
per ml
Not more than 5 x102 CFU per g or
per ml
Not more than102 CFU per g or per
ml
Absent in 25g or 25 ml
Absent in 1 g or 1 ml
C
Not more than 5 x 105 CFU per g or
per ml
Not more than 5 x 104 CFU per g or
per ml
Not more than 5 x 104 CFU per g or
per ml
Absent in 25 g or 25 ml
Absent in 1 g or 1 ml

Chromatography and spectral methods
Chromatographic methods used to assess the chemical stability of
herbal products include thin layer chromatography (TLC), high (ultra)
performance liquid chromatography (HPLC, UPLC), high performance-
thin layer chromatography (HP-TLC), gas liquid chromatography
(GLC), etc., while spectral methods used include ultraviolet-visible
(UV-VIS) spectroscopy, infrared (IR) spectroscopy, nuclear magnetic
resonance (NMR) and mass spectroscopy (MS). These techniques
allow tracing of changes which may occur during storage of a complex
mixture of biologically active substances contained in herbal materials.
Comparisons of appropriate characteristic/fingerprint chromato-
grams allow the determination of the stability of identified active
ingredients (if any) and other substances present in the finished
herbal product (which may appear as markers) [10, 38, 66].
Assessment of safety parameters
The acute toxicity of the herbal medicinal product may be assessed
at the beginning and end of the stability study for products used in
the treatment of acute conditions. Subchronic and chronic toxicity
studies may also be done for products meant for the treatment of
chronic conditions [27, 67]. However, due to the time is taken in
doing such studies, they should be determined on a case by case
basis depending on the nature of the herbal medicinal product
involved with consideration to other already determined
parameters. These tests if not possible for inclusion in a stability
study should be used as quality control measures or tests [64, 68].
Conditions for stability testing of products
The shelf-life of a product depends on its storage temperature and
also on humidity. These conditions may vary from country to
country. Four climatic zones have been defined in order to enhance
determination of stability testing conditions for products (table 2).
The definition is based on observed temperatures and relative
humidity, both inside and outside rooms, from which mean
temperatures and average humidity values are calculated [8]. The
general conditions for testing products in various containers and
storage temperatures are shown in tables 3-6.

Table 2: Temperature and humidity distribution in climatic zones

Climatic zone Climate Mean temperature Average humidity
I Temperate 21 60
II Subtropical 26 65
III Tropical (dry) 31 60
IV Tropical (wet) 31 70
Aulton [8], I-Temperate climate includes Canada, New Zealand, Northern Europe, United Kingdom and Russia, II-Mediterranean and subtropical
climate includes Japan, Southern Europe and the USA, III-Hot and dry climate includes Argentina, Australia, Botswana and the Middle East, IV-Hot
and Humid Brazil, Ghana, Indonesia, Nicaragua, Nigeria and the Philippines

Table 3: General conditions for testing of products (impermeable containers)

Study Storage conditions Time points for testing Minimum data covered at submission
Long term 25 °C±2 °C/60% RH± 0, 3, 6, 12, 18, 12 mo
5% RH or 30 °C±2 °C/65% RH±5% RH 24, 36, 48, 60
Intermediate 30 °C±2 °C/65% RH±5% RH 0, 1, 3, 6 6 mo
Accelerated 40 °C±2 °C/65% RH±5% RH 0, 1, 3, 6 6 mo

Table 4: Conditions for testing of products in semipermeable containers*

Study Storage conditions Time points for testing Minimum data covered at submission
Long term 25 °C±2 °C/40% RH±5% RH or 30 °C±2 °C/35% 0, 3, 6, 12, 18, 12 mo
RH±5% RH 24, 36, 48, 60
Intermediate 30 °C±2 °C/35% RH±5% RH 0, 1, 3, 6 6 mo
Accelerated 40 °C±2 °C/not more than 25% RH±5% RH 0, 1, 3, 6 6 mo
Accelerated 40 °C±2 °C/75% RH±5% RH 0, 1, 3, 6 6 mo
*Alternatively for products in semipermeable containers, samples may be stored under general conditions like that of impermeable containers and
water loss calculated by determining permeation coefficient or using calculated ratio of water loss

Table 5: Conditions for testing of products intended for storage in a refrigerator

Study Storage conditions Time points for testing Minimum data covered at submission
Long term 5 °C±3 °C 0, 3, 6, 12, 18, 24, 36, 48, 60 12 mo
Accelerated 25 °C±2 °C/60% RH±5% RH 0, 1, 3, 6 6 mo
If significant change occurs between 3 and 6 mo at accelerated storage conditions then shelf life based on real time data should be conducted in the long term

5
 Kwakye et al.
J Crit Rev, Vol 4, Issue 4, 1-8

Table 6: Conditions for testing of products intended for storage in a freezer

Study Storage conditions Time points for testing Minimum data covered at submission
Long term -20 °C±5 °C 0, 3, 6, 12, 18, 12 mo
24, 36, 48, 60

The stability study should be conducted in the container closure system
in which it will be marketed [8, 10, 64, 69]. In general, “significant
change” for a finished herbal product may be defined as a 10 % change
in assay from its initial value with respect to the marker being used; or
failure to meet the acceptance criteria for potency when using biological
or immunological procedures; any degradation product exceeding its
acceptance criterion; failure to meet the acceptance criteria for
appearance, physical attributes, and functionality test (e. g., colour, phase
separation, re-suspendibility, caking, hardness, dose delivery per
actuation, pH). It should be noted that accelerated stability tests may
cause some dosage forms such as ointments and creams to change form
due to the relatively high temperatures to be employed. This should not
be mistaken for the failure of the product to meet acceptance criteria
since such changes should be expected [8, 10, 38, 70].
Evaluation of stability data
A systematic approach should be adopted in the presentation and
evaluation of the stability information. This should include results
from the physical, chemical, biological, and microbiological tests,
including particular attributes of the dosage form (for example,
dissolution rate for solid oral dosage forms), where appropriate
[69]. The stability study should help establish the shelf life of
future batches of an herbal medicine based on testing a minimum
of two or three batches. The degree of variability of individual
batches affects the confidence that a future production batch will
remain within specification throughout its shelf life. Where the
data show so little degradation and so little variability that it is
apparent from looking at the data that the requested shelf life will
be granted, it is normally unnecessary to go through the formal
statistical analysis. The overall shelf life should be based on the
minimum time a batch can be expected to remain within
acceptance criteria. The evaluation should consider not only the
assay but also the degradation products and other appropriate
attributes [9, 10, 69, 70, 71, 72].
The level of selected markers and possible degradation products
should also be ascertained with time in order to help determine the
shelf-life of the products. Depending on the availability of
equipment, selected tests such as TLC, HPLC, HPTLC, UV-Visible
spectrophotometry may be used to quantify selected markers as
well as determine the levels of degradation products. It is not
expected that every listed test be performed at each time point. The
list of tests presented for each dosage form is not intended to be
exhaustive, nor is it expected that every listed test be included in the
design of a stability protocol for a particular finished herbal product
[8, 9, 10, 72]. Table 7 presents some recommended stability tests for
various herbal dosage forms.

Table 7: Recommended stability tests for different herbal dosage forms

Type of dosage form Recommended stability tests
Decoctions (oral), Change in colour, odour, taste, formation of a precipitate, clarity, specific gravity, total solid residue, pH, viscosity,
Glycerites, Aceterites, extractable, phytochemical constituents, microbial contamination, preservative efficacy/challenge tests, and
oxymels toxicity/safety [14].
Tablets Change in colour, pH, total water or solvent extractive, phytochemical constituent, dissolution (or disintegration, if
justified), water content, hardness, friability, swelling, crakes and clumping (coated tablets), microbial contamination,
preservative efficacy/challenge tests, toxicity/safety [14].
Capsules Change in colour, pH, total extractive, phytochemical constituent, brittleness, hardening or softening of shell, dissolution
(or disintegration, if justified), water content, microbial contamination, preservative efficacy/challenge tests, toxicity.
Alcoholic beverages, Clarity, pH, specific gravity, alcohol content, extractable, change in colour, odour, taste, the formation of a precipitate,
Tinctures total solid residue, extractable, phytochemical constituents, microbial contamination, toxicity.
Teas and powders Change in odour, moisture content, pH, total water extractive, formation of hard mass, caking,
Phytochemical constituents, microbial contamination, and toxicity.
Ointment, balms Change in colour, odour, homogeneity, pH, consistency, grittiness, excessive bleeding, phytochemical constituents,
microbial contamination, and toxicity.
Oils Rancidity, change in colour, odour, pH, phytochemical constituents, microbial contamination, toxicity
Pastes and creams Change in colour, odour, homogeneity, pH, consistency, grittiness, cracking, shrinking due to evaporation of water,
phytochemical constituents, microbial contamination, preservative challenge tests (where preservative are used), toxicity
Soaps Change in colour, odour, homogeneity, pH, phytochemical constituents, microbial contamination, preservative
challenge tests (where preservative are used), toxicity/skin sensitivity tests
Suppositories and Softening, hardening or drying, dissolution
Pessaries

CONCLUSION REFERENCES
Herbal products have gained wide acceptance in both developing 1.
and advanced countries and are being produced in commercial
quantities. The stability of these herbal products is of paramount
importance to assure product quality, safety and efficacy. It is 2.
expected that herbal product manufacturers will apply the
necessary protocols and techniques to achieve and maintain the
stability of their products during manufacture, storage, 3.
transportation and usage. This will contribute to patient safety,
product efficacy and enhance patient confidence in herbal products
and improve compliance. 4.
CONFLICT OF INTERESTS
The authors declare no conflict of interest regarding the publication 5.
of this paper.
Ekor M. The growing use of herbal medicines: issues relating to
adverse reactions and challenges in monitoring safety. Front
Pharmacol 2014;4:177.
Thakur L, Ghodasra U, Patel N, Dabhi M. Novel approaches for
stability improvement in natural medicines. Pharmacogn Rev
2011;5:48-54.
Dodoo ANO, Appiah-Dankwah A, Gyansa-Lutterodt M,
Duwiejua M. Safety monitoring of herbal medicines in Ghana:
challenges and opportunities. Drug Safety 2006;29:352.
Mukherjee PK, Houghton PJ. Evaluation of Herbal Medicinal
Products-Perspectives on quality, safety and efficacy. London,
UK, Pharmaceutical Press; 2009.
Mukherjee PK. Evidence-Based Validation of Herbal Medicine.
1st ed. Netherlands: Elsevier; 2015.

6
 Kwakye et al.
6. Benzie IFF, Wachtel-Galor S. Herbal Medicines, Biomolecular
and Clinical Aspects. 2nd ed. New York: CRC Press; 2011.
7. Gafner S, Bergeron C. The challenges of chemical stability testing
of herbal extracts in finished products using state-of-the-art
analytical methodologies. Curr Pharm Anal 2005;1:203-15.
8. Aulton ME. Aulton’s pharmaceutics-the design and
manufacture of medicines. 3rd ed. London: Churchill
Livingstone; 2007.
9. World Health Organization (WHO). Stability Testing of Active
Substances and Pharmaceutical Products. Restricted Working
document QAS/06.179; 2006. p. 10-32.
10. European Medicines Agency (EMA). Reflection paper on
stability testing of herbal medicinal products and traditional
herbal medicinal products. EMA/HMPC/3626/2009 Committee
on Herbal Medicinal Products (HMPC); 2009.
11. European Pharmacopoeia. Vol. 1. Herbal drug preparations;
2005.
12. Green J. The Herbal medicine-makers Handbook: A Home
Manual. USA: Crossing Press; 2002.
13. Yi YD, Chang LM. An overview of traditional Chinese herbal
formulae and a proposal of a new code system for expressing
the formulae titles. J Evidence-Based Complementary Altern
Med 2004;1:125-32.
14. Ghiware Nitin B, Gattani Surendra G, Chalikwar Shailesh S.
Design, development and evaluation of oral herbal
formulations of Piper nigrum and Nyctanthes arbortristis. Int J
PharmTech Res 2010;2:171-6.
15. Bone K, Mills S. Principles and practice of phytotherapy:
modern herbal medicine. 2nded. Elsevier Health Sciences; 2013.
16. Hoffman D. Medical Herbalism: The Science and Practice of
Herbal Medicine. Vermont: Healing Arts Press; 2003.
17. Liu Y, Yang J, Cai Z. Chemical investigation on Sijunzi decoction
and its two major herbs Panax ginseng and Glycyrrhiza
uralensis by LC/MS/MS. J Pharm Biomed Anal 2006;41:1642-7.
18. Chewchinda S, Wuthi-udomlert M, Gritsanapan W. HPLC
quantitative analysis of rhein and anti dermatophytid activity
of cassia fistula pod pulp extracts of various storage conditions.
BioMed Res Int 2013. http://dx.doi.org/10.1155/2013/
821295
19. Bascom A. Incorporating Herbal Medicine into Clinical Practice.
Philadelphia: F. A. Davis Company; 2002.
20. Politi M, Zloh M, Pintado ME, Castro PML, Heinrich M, Prieto JM.
Direct metabolic fingerprinting of commercial herbal tinctures
by nuclear magnetic resonance spectroscopy and mass
spectrometry. Phytochem Anal 2009;20:328-34.
21. Bone K. Dosage considerations in herbal medicine Part 3.
Mediherb Professional Review; 1993. Available from:
http://www.mediherb.com/media/276930/prno33.pdf. [Last
accessed on 25th Aug 2016]
22. Morgan M. Ethanol in medicine–a phytotherapist’s perspective;
2009, p. 1-4.
23. Bruton-Seal J, Seal M. Backyard medicine-harvest and make
your own herbal remedies. New York: Skyhouse Publishing;
2009.
24. Bilia AR, Bergonzi MC, Gallori S, Mazzi G, Vincieri FF. Stability of
the constituents of Calendula, Milk-thistle and Passionflower
tinctures by LC-DAD and LC-MS. J Pharm Biomed Anal
2002;30:613-24.
25. Beal GD, Walters KL, Block Jr P. Stability of iodine solutions and
tinctures. J Pharm Sci 1947;36:203-7.
26. Peschel W. Quality control of traditional cannabis tinctures:
pattern, markers, and stability. Sci Pharm 2016;84:567-84.
27. Ogbonnia SO, Mbaka GO, Igbokwe NH, Anyika EN, Alli P,
Nwakakwa N. Antimicrobial evaluation, acute and subchronic
toxicity studies of Leone Bitters, a Nigerian polyherbal
formulation, in rodents. Agric Biol J North Am 2010;1:366-76.
28. Komes D, Belscak-Cvitanovic A, Horzic D, Drmic H, Skrabal S,
Milicevic B. Bioactive and sensory properties of herbal spirit
enriched with cocoa (Theobroma cacao L.) polyphenolics. Food
Bioprocess Tech 2012;5:2908-20.
29. Buglass AJ. Handbook of alcoholic beverages: technical, analytical
and nutritional aspects. Vol. I. Wiley Publications; 2011.
30. Karabegovic IT, Vukosavljevic PV, Novakovic MM, Gorjanovic
SZ, Dzamic AM, Lazic ML. Influence of the storage on bioactive
J Crit Rev, Vol 4, Issue 4, 1-8
compounds and sensory attributes of herbal liqueur. Digest J
Nanomaterials Biostructures 2012;7:1587-98.
31. Rodriguez M, Sadler GD, Sims CA, Braddock RJ. Chemical
changes during storage of an alcoholic orange juice beverage. J
Food Sci 1991;56:475-9.
32. Winfield AJ, Rees AJ, Smith I. Pharmaceutical practice. London:
Churchill Livingstone; 2009.
33. Bayor MT, Johnson R, Gbedema SY. The oral capsule-the most
appropriate dosage form for Croton membranaceus. Int J Pharm
Sci Res 2011;2:55-62.
34. Johnson R, Bayor MT, Adotey J. Formulation and evaluation of
Bridelia ferruginea and Canthium glabriflorum herbal capsules.
J Herbal Med Plants 2010;1:18-22.
35. Bankoti K, Rana MS, Bharadwaj MK. Accelerated stability study
of herbal capsules. IOSR J Pharm 2012;2:1-6.
36. Pranskuniene Z, Bernatoniene J, Kalveniene Z, Masteikova R,
Mekas T, Velziene S, et al. New formula herbal pellets
demonstrate a uniform and stable release of the active
ingredients in vitro. Acta Pol Pharm 2013;70:727-36.
37. Daberte I, Barene I, Rubens J, Daugavietis M, Sazhenova N.
Stability of soft gelatin capsules containing thick extract of pine
needles. Medicina (Kaunas) 2011;47(Suppl 2):71-7.
38. Mishra US, Murthy PN, Sahoo SK, Sahu KC. Formulation and
evaluation of herbal tablet containing methanolic extract of
Calophyllum inophyllum. Int J Pharm 2012;2:181-6.
39. Kucinskaite A, Sawicki W, Briedis V, Sznitowska M. Fast
disintegrating tablets containing Rhodiola rosea L. Extract Acta
Pol Pharm 2007;64:63-7.
40. Al-Achi A. An introduction to botanical medicines: History, Science,
Uses and Dangers. Connecticut: Praegers Publishers; 2008.
41. Zdoryk OA, Khokhlova KO, Georgiyants VA, Vyshnevska LI.
Investigation of physical and chemical stability of ointment
with herbals. Int J Pharm Compd 2014;18:248-52.
42. Vincent WM. The complete guide to growing healing and
medicinal herbs: Everything you need to know simply
explained. Atlantic publishing company; 2011.
43. Russell ND, LW Sneyd LW. Healthy solutions: a guide to simple
healing and healthy wisdom. Basic Health Publications Inc.
USA; 2006.
44. Turek C, Stintzing FC. Stability of essential oils: a review. Compr
Rev Food Sci Food Saf 2013;12:40-53.
45. Jones M. The Complete Guide to Creating Oils, Soaps, Creams,
and Herbal Gels for your Mind and Body. Atlantic Publishing
Company; 2011.
46. Grosso A. The Everything Soapmaking Book: Learn How to
Make Soap at Home with Recipes. Massachusetts: Adams
Media; 2013.
47. Panda H. Herbal soaps and detergents handbook. Natl Institute
Industrial Res 2000;1:194-6.
48. Van Loveren C. Toothpastes. Amsterdam: Karger Medical and
Scientific Publishers; 2013.
49. Packer L, Ong CN, Halliwell B. Herbal and Traditional Medicine,
Molecular Aspects of Health. New York: Marcel Dekker; 2004.
50. Bouwman Y, Fenton-May V, Le Brun P. Practical Pharmaceutics,
An International Guideline for the Preparation, Care and Use of
Medicinal Products. Netherlands: Springer; 2015.
51. Tiwari M. Ayurveda: the secrets of healing. Delhi: Motilal
Banarsidass Publishers, India; 1995.
52. Castleman M. The New Healing Herbs: The Classic Guide to
Nature's Best Medicines. Rodale Inc., USA; 2001.
53. Ameh S, Obodozie O, Gamaniel S, Abubakar M, Garba M.
Physicochemical variables and real time stability of the herbal
substance of Niprd-AM1®-an antimalarial developed from the
root of Nauclea latifolia S. M. (Rubiaceae). Int J Phytomed
2010;2:332-40.
54. Page L. Linda Page’s Healthy Healing; a guide to self-healing for
everyone. 12th ed. Healthy healing Inc; 2004.
55. Philips N, Philips M. The Herbalist's Way: The Art and Practice
of Healing with Plant Medicine. Chelsea Green Publishing;
2005.
56. Shao L, Chow SC. Drug shelf-life estimation. Stat Sin
2001;11:737-45.
57. Kruse SO. Stability testing of herbal medicinal products;
Bridging Science to Industry. Planta Med; 2013. p. 79-PK15.
7
 Kwakye et al.
58. Gautam A, Kashyap SJ, Sharma PK, Garg VK, Visht S, Kumar N.
Identification, evaluation and standardization of herbal drugs:
a review. Pharm Lett 2010;2:302-15.
59. Awang DVC. Standardization of herbal medicinal products. Acta
Hort 2004;629:112-4.
60. Bodhisattwa M, Nagori BP, Rambir S. Recent trends in herbal
drugs: a review. Int J Drug Res Tech 2011;1:17-25.
61. Jain SK. Stability protocols for different dosage forms.
Department of Pharmacy, Institute of Biomedical Education
and Research, Magalayatan University; 2011. Available from:
http://www.slideshare.net/sachin1409/stability-protocols-
for-different-dosage-forms-by-sachin-jain. [Last accessed on
18th Aug 2016]
62. Joshi DD. Herbal drugs and fingerprints: evidence based herbal
drugs. Springer Sciences and Media; 2012.
63. Ngoc ATP. The microbiological requirements of a stability
study. AMS Laboratories Pty Ltd; 2012. p. 6-15. Available from:
http://www.amslabs.com.au/WS/files/54/546be2aa-bdbe-
43e3-84af-d44f9114a599.pdf [Last accessed on 18th Aug 2016]
64. Food and Drugs Authority (FDA), Ghana. Guidelines for
Registration of Herbal Medicinal Products in Ghana.
FDA/HMD/GL-HB/2012/01 2013;1:5-7.
65. British Pharmacopoeia. Vol. IV. Herbal Drugs, Herbal Drug
Preparations and Herbal Medicinal products. British
Pharmacopoeia Commission, MHRA, London; 2013.
66. Chhetri HP, Yogol NS, Sherchan J, Anupa KC, Mansoor S, Thapa P.
Formulation and evaluation of antimicrobial herbal ointment.
Kathmandu University J Sci Eng Technol 2010;6:102-7.
View publication stats
J Crit Rev, Vol 4, Issue 4, 1-8
67. Lam YWF, Huang SM, Hall SD. Herbal supplements–drug
interactions: scientific and regulatory perspectives. New York:
CRC Press, USA; 2006.
68. Leung PC. A comprehensive guide to Chinese medicine. 2nd ed.
World Scientific; 2015.
69. ICH Q1 AR2, Stability testing guidelines: stability testing of new
drug substances and products. Available from: http://
www.ikev.org/haber/stabilite/kitap/29%201.1%20Stability%
20Workshop%20ICH%20Q1AR2%20C.pdf. Last accessed on
18th Aug 2016].
70. Guidelines on specifications, test procedures and acceptance
criteria for herbal substances, herbal preparations and herbal
medicinal products/traditional herbal medicinal products’
(CPMP/QWP/2820/00, EMEA/CVMP/815/00, current version).
Available from: http://www.ema.europa.eu/docs/ en_GB/
document_library/Scientific_guideline/2009/09/WC50000339
3.pdf. [Last accessed on 23rd Aug 2016].
71. Ahuja S, Scypinski S. Handbook of modern pharmaceutical
analysis. 2nd ed. Academic Press; 2011.
72. Zahn M, Kållberg PW, Slappendel GM, Smeenge HM. A risk-
based approach to establish stability testing conditions for
tropical countries. J Pharm Sci 2006;95:946-65.
How to cite this article
• Doriskumadoh, Kwabena Ofori-Kwakye. Dosage forms of
herbal medicinal products and their stability considerations-an
overview. J Crit Rev 2017;4(4):1-8.
 Semester- 6th
Subject: Herbal Drug Technology

Subject code: BP603

Module - 3

Herbal Cosmetics
Objectives: upon compilation of this module the student should be able to:

1. Know the herbal cosmetics, natural sweeteners and herbal excipients

2. Understand about the methods for preparation and evaluation methods of herbal cometics
3. Know about the novel drug delivery systems like Phytosomes

Learning outcomes: the student will be able to:

1. Learn the sources and description of raw materials for herbal origin used as a fixed oil,
colorants, antioxidants, hair care and dental care.
2. Learn about the significance of herbal excipients.
3. Learn about the standardization of herbal formulations.
4. Learn about the novel drug delivery system like Phytosomes and their advantages over
herbal extracts.

Introduction: The concept of beauty and cosmetics dates back to ancient mankind and
civilization. Generally herbal cosmetics are also referred to as natural cosmetics. Herbal
cosmetics are formulated, using different cosmetic ingredients to form the base in which one or
more herbal ingredients are used to cure various skin ailments. Plants are highly used for
development of new drug products for cosmeceuticals and pharmaceutical applications. Herbal
cosmetics are the products in which herbs are used in crude or extract form. Herbal Cosmetics,
referred as Products, are formulated, using various permissible cosmetic ingredients to form the
base in which one or more herbal ingredients are used to provide defined cosmetic benefits only,
shall be called as “Herbal Cosmetics”. Herbs do not produce instant cures. They offer a way to
put the body in proper tune with nature. A huge number of cosmetic and toiletry formulations
have been designed and developed based upon Indian Herbs recently. Other than traditionally
documented applications, some modern trials have also been using the utility of Indian herbs in
Personal Care products. The demand of herbal medicines is increasing apidly due to their skin
friendliness and lack of side effects. The best thing of the herbal cosmetics is that it is purely
made by the herbs and shrubs and thus is side-effects free. The natural content in the herbs does
not have any side effects on the human body; instead provide the body with nutrients and other
useful minerals. The term Cosmeceuticals was first used by Raymond Reed founding member of
U.S Society of Cosmetics Chemist in 1961. He actually used the word to brief the active and
science based cosmetics.

Natural products: The name itself suggests that herbal cosmetics are natural and free from all
the harmful synthetic chemicals which otherwise may prove to be toxic to the skin. Instead of
traditional synthetic products different plant parts and plant extracts are used in these products,
e.g. aloe-vera gel and coconut oil. They also consist of natural nutrients like Vitamin E that
keeps skin healthy, glowing and beautiful. For example, Aloevera is a herbal plant
species belonging to liliaceae family and is naturally and easily available. There are a rising
number of consumers concerned about ingredients such as synthetic chemicals, mineral oils who
demand more natural products with traceable and more natural ingredients, free from harmful
chemicals and with an emphasis on the properties of botanicals.

Skincare Products:
Coconut oil: It is produced by crushing copra, the dried kernel, which contains about 60-65% of
the oil. Coconut oil contains a high amount of glycerides of lower chain fatty acids. Coconut oil
is derived from the fruit or seed of the coconut palm tree Cocos nucifera, family Arecaceae. The
melting point of coconut oil is 24 to 25°C (75-76ºF) and thus can be used easily in liquid or solid
forms and is often used in cooking and baking. Coconut oil is excellent as a skin moisturizer and
softener.

Sunflower oil: It is the non-volatile oil extracted from sunflower seeds obtained from Helianthus
annuus, family Asteraceae. Sunflower oil contains lecithin, tocopherols, carotenoids and waxes.
It hassmoothing properties and is considered non-comedogenic. A simple yet cost-effective oil,
well tried and tested for generations in a wide variety of emulsions formulated for face and body
Products.

Jojoba oil: It is a mixture of long chain, linear liquid wax esters extracted from the seeds of the
desert shrub Simmondsia chinenesis, family simmondsiaceae. Jojoba oil is easily refined to
remove any odor, color it is oxidatively stable, and is often used in cosmetics as a moisturizer
and as a carrier oil for exotic fragrances. Human sebum and jojoba oil are virtually identical.
Sebum protects and moisturizes the skin and hair but is stripped away by chemicals, pollutants,
sun and the aging process, resulting in dry skin and hair. Jojoba oil replenishes what skin and
hair lose and restores them to their natural pH balance.

Olive oil: This oil is a fixed oil extracted from the fruits of olea europaea, family oleaceae. The
major constituents are triolein, tripalmitin, trilinolein, tristearate, monosterate, triarachidin,
squalene, β-sitosterol and tocopherol. It is used as skin and hair conditioner in cosmetics like
lotions, shampoos etc. It is a potent fatty acid penetration enhancer.

Aloevera: Aloevera is a herbal plant species belonging to liliaceae family that is found only in
cultivation, having no naturally occurring populations, although closely related aloes do have
presence in northern Africa. It is an ingredient in many cosmetics because it heals, moisturizes,
and softens skin. Simply cut one of the aloe vera leaves to extract the soothing gel. Aloe vera
contains amino acids like leucine, isoleucine, saponin glycosides that provide cleansing action,
vitamins A,C,E,B, choline, B12 and folic acid and provide antioxidant activity.

Anti-aging Herbs
Rhodiola rosea- It is commonly known as golden root, roseroot, Aaron's rod, arctic root, king's
crown, lignum rhodium, orpin rose. It is a plant in the Crassulaceae family that habitats in cold
regions of the world. Traditional folk medicine used R. rosea to increase physical endurance,
work productivity, longevity, resistance to high altitude sickness, and to treat fatigue, depression,
anemia, impotence, gastrointestinal ailments, infections, and nervous system disorders. R. rosea
is rich in phenolic compounds, known to have strong antioxidant Properties.

Carrot: It is obtained from the plant Daucus carota belonging to family Apiaceae. It is a
valuable herb since ages as due to its richness in Vitamin A along with other essential vitamins.
Carrot seed oil is used as anti-aging, revitalizing and rejuvenating agent. The carrot gets its
characteristic and bright orange colour from β-carotene, and lesser amounts of α-carotene and γ-
carotene. α and β-carotenes are partly metabolized into vitamin A in humans.

Gingko: In China and Japan, the leaves and nuts of the Ginkgo biloba (G. biloba) tree have been
used for thousands of years to treat various medical conditions, including poor blood circulation;
hypertension; poor memory, and depression, particularly among the elderly; male impotence. In
addition, it is gaining a similar reputation as an antioxidant and anti-inflammatory agent. Ginkgo
biloba belongs to family Ginkgoaceae, which grows to a huge size.

Neem: Neem or Margosa is a botanical relative of mahogany. It belongs to the family Meliaceae.
The Latinized name of NeemAzadirachta indica-is derived from the Persian. Azad=Free,
dirakht=Tree, i-Hind=of Indian Origin. The common treatment for the dandruff is Neem as it
produces antifungal, antibacterial, pain-relieving, and anti- compounds that would treat dandruff.

Dandruff treatment:

Ayurveda has numerous natural medications wherein the most common herbs include Neem,
Kapoor (naphthalene), and Henna, Hirda, Behada, and Amalaki, Magic nut, Bringaraj, Rosary
Pea, Sweet Flag, Cashmere tree and Mandor.

Henna: Henna comes from the plant Lawsonia inermis family Lythraceae, which contain a dye
molecule called Lawsone, which when processed produces Henna powder. Besides lawsone
other constituents present are gallic acid, glucose, mannitol, fats, resin (2%), mucilage and traces
of an alkaloid. Leaves yield hennatannic acid and an olive oil green resin, soluble in ether and
alcohol. Lawsone osisolated from the leaves of L.inermis has shown significant antifungal antibiotic
effect.
Shikakai: Acacia concinna Linn. (Leguminosae) is a medicinal plant that grows in tropical
rainforests of southern Asia. The fruits of this plant are used for washing hair, for improving hair
growth, as an expectorant, emetic, and purgative. The powder of Acacia Concinna Linn shows
the presence of saponins, alkaloid, sugar, tannin, flavanoids, anthraquinone glycosides.

Hair-care

Amla: Amla is the name given to the fruit of a small leafy tree (Emblica Officinalis), which
grows throughout India and yields characteristics. edible fruit. It is highly praised both for its
high vitamin C content and for the precious oil, which is extracted from its seeds and pulp and
used as a treatment for hair and scalp problems. It is used in eye syndromes, hair loss, and
children ailments etc.

Rose: There are mainly four species of roses for oil production. These are Rosa damascena Mill.,
R. gallica L., R. moschata Herrm. and R. centifolia L. Rose oil and rose water have many
therapeutic effects. Rose oil helps soothe the mind and heals depression, grief, nervous stress and
tension. It also helps to heal wound and skin health.

Eucalyptus oil: There are around 700 different species of Eucalyptus in the world, of which at
least 500 produceatypeofessential oil. It is produced by steam distillation from the leaves of
Eucalyptus species (E. cinerea F. Muell., E. baueriana F. Muell., E. smithii R. T. Baker, E.
bridgesiana R. T. Baker, E. microtheca F. Muell., E. foecunda Schau., E. pulverulenta Sims, E.
propinqua Deane and Maiden, E. erythrocorys F. Muell.) etc. They are widely used in the
preparation of liniments, inhalants, cough syrups, ointments, toothpaste and also as
pharmaceutical flavors. The European Pharmacopoeia monograph for Eucalyptus oil sports a
chromatographic profile: 1,8-cineole (eucalyptol; not less than70%), limonene (4- 12%), α-
pinene (2-8%), α- phellandrene (less than 1.5%), β-pinene (less than 0.5%), camphor (less than
0.1%) .

Grape seeds: It promotes proliferation of hair follicle cells invitro and that they possess
remarkable hair cycle converting activity from the telogen phase to anagen phase invivo.

Ginkobiloba: This leaf extract also promotes hair regrowth through combined effects on
proliferation and apoptosis of the cells in the hair follicle, thus suggesting potential as a hair
tonic.

Aloe: Aloe gel is used traditionally for hair loss and for improvement in hair growth following
alopecia. Aloenin is the major constituent responsible for promoting hair growth without
irritating the skin.
Oral care: Oral health/dental health is an inseparable part of general health. Oral health has an
effect on general health as it causes considerable pain and suffering. It has an impact on a
person's speech, selection of food, quality of life, and well-being. In view of the prevalence of
oral diseases, their impact on individuals and society, and the expense of their treatment, oral
diseases may be considered a major public health problem and they are listed among the most
common of the chronic diseases that affect mankind. Oral diseases are the fourth most expensive
diseases to treat in certain countries. According to the World Health Organization (WHO) report,
dental caries, though exhibiting a declining trend in many parts of the industrialized world, is
still an important public health concern in many developing countries. The statistics suggest that
dental caries affect 60-90% of schoolgoing children in developing countries. Loss of teeth
because of periodontitis often causes discomfort, and compromises the esthetics and function.
Moreover, recent studies suggest an association between chronic low-grade infections such as
periodontitis and systemic health problems (preterm low birth weight, cardiovascular diseases,
diabetes mellitus, and chronic obstructive pulmonary disease).There is an immediate need for
promoting preventive strategies that are socially acceptable, easily available, and at the same
time be cost-effective. This calls for the evolution of innovative strategies that are robust,
efficient, and feasible.

Clove oil: Cloves are the aromatic flower buds of a tree in the Myrtaceae family, Syzygium
aromaticum. In the past cloves were used as a remedy to ease the pain of toothache. Clove oil has
a local anaesthetic effect and temporarily numbs and relieves pain. It is used in the preparation of
some tooth pastes and in Clovacaine solution, a local anaesthetic used in oral ulceration and
inflammation. Eugenol, which is extracted from essential oils including clove oil, is also mixed
with zinc oxide to form temporary tooth restorations.

Eucalyptus saligna mouthwash gargle is used in Cameroon to treat mainly toothache, sore
throat and halitosis. It has been shown that the essential oil of the leaves of Eucalyptus globulus
has antimicrobial activity against gram-negative bacteria (E. coli) as well as gram-positive
bacteria (S. aureus) which are found in the oral cavity.

Moringa oleifera roots are also used to treat toothache in Cameroon by direct application on the
tooth cavity. This plant has been found to be specific against Staph. Aureus, Vibrio cholerae, and
Escherichia coli and have no antifungal activity. Its antibacterial activity is responsible for its
ability to calm toothache.

Allium sativum: It is one of the most extensively researched medicinal plants with a typical
odor. Its antibacterial activity depends on allicin produced by enzymatic activity of allinase on
allicin produced by enzymatic activity of allinase on allicin after crushing or cutting garlic clove.
Garlic extract inhibits the growth of Streptococcus mutans, and therefore can be used as an
effective remedy in the prevention of dental caries when used it is used as a constituent in
toothpaste or mouthwash.

Tulsi (Ocimum sanctum): Tulsi consists of tannins (4.6%) and essential oil (up to 2%), eugenol
(up to 62%), methyleugenol (upto 86%), and α- and β-caryophyllene (up to 42%),
methylchavicol, linalool and 1,8-cineole. It has got antihelminthic, analgesic, antipyretic,
immune stimulatory, antiulcer, antimicrobial, anti – inflammatory property. Used in
periodontitis. Contraindicated in pregnant and lactating women, used with caution in children.

Green Tea (Camellia sinensis): Green tea contains polyphenol contents comprising catechin
(C), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC) epicatechingallate (ECG),
and epi-gallocatechingallate. It is anti-inflammatory, antibacterial, anti-viral. Used in the
treatment of periodontal disease.

Marigold (Calendula officinalisL.) It is native to the Mediterranean areas. It is used for the
treatment of skin disorders and pain, to facilitate healing after oral surgery and in oral cavity
inflammations. It has also anti-edematous activity.

Grape Seed Extract: Grape seed extract contains pro-anthocyanidins (PA) which are potent
antioxidants and are known to possess anti-inflammatory, antibacterial and immune-stimulating
effects. It has been reported to strengthen collagen based tissues by increasing collagen cross-
links. In a study conducted to determine re-mineralizing effects of grape seed extract on artificial
root caries, results showed that is a promising natural agent for noninvasive root caries therapy.

Papaine: Papaine is a proteolytic enzyme that comes from the latex of the leaves and fruits of
the green adult papaya. It has an anti-inflammatory, bacteriostatic, bactericidal characteristic and
is effective against gram positive and gram negative organisms. Similar to human pepsin,
papaine acts as a chemical debridement ant-iinflammatory agent, which does not damage healthy
tissues and accelerates cicatrization process. Papaine acts only in infected tissue as it lacks a
plasmatic antiprotease called α-1-anti-trypsin.

Meswak: It is a derivative from Arak tree, is used by many people in different cultures as
traditional toothbrush for oral hygiene. The meswak extract has also found its way into the
dentrifrices in the recent years as antiplaque and antigingivitis agents. Chewing sticks should be
obtained from fresh stems of medicinal plants.
 Herbal Excipients
Excipients are defined as ‘the substance used as a medium for giving a medicament. The
specific application of natural polysaccharide polymers in pharmaceutical formulations
include to aid in the processing of the drug delivery system during its manufacture,
protect, support or enhance stability, bioavailability or patient acceptability, assist in product
identification, or enhance any other attribute of the overall safety, effectiveness or
delivery of the drug during storage or use. Several pharmaceutical excipients of plant
origin, like starch, agar, alginates, carrageen an, guar gum, xanthan gum, gelatin, pectin,
acacia, tragacanth, and cellulose find applications in the pharmaceutical industry as binding
agents, disintegrates, sustaining agents, protective’s, colloids, thickening agents, gelling
agents, bases in suppositories, stabilizers, and coating materials.
ADVANTAGE OF HERBAL EXCIPIENTS

Biodegradable: Naturally occurring polymers produced by all living organisms. They show no
adverse effects on the environment or human being.

Biocompatible and non-toxic: Chemically, nearly all of these plant materials are
carbohydrates in nature and composed of repeating monosaccharide units. Hence they are
non-toxic.

Economic: They are cheaper and their production cost is less than synthetic material.

Safe and devoid of side effects: They are from a natural source and hence, safe and
without side effects.

Easy availability: In many countries, they are produced due to their application in many
industries.

CLASSIFICATION OF EXCIPIENTS:

Excipients are commonly classified according to their application and function in the drug
products:

Herbal Sweetners

Binders, diluents

Disintegrants

Colorants

Viscosity builders

Perfumery agents and flavoring agents

Herbal sweetners:
1. Stevia: It is a very popular low-calorie sweetener.It’s extracted from the leaves of a plant
called Stevia rebaudiana. Several sweet compounds are found in stevia leaves. The main
ones are stevioside and rebaudioside A. Both are hundreds of times sweeter than sugar,
gram for gram.Therefore, stevia is very sweet but has virtually no calories. Additionally,
a few human-based studies suggest stevia has health benefits. Stevia can lower high
blood pressure in people with hypertension by 6–14%. However, it has no effect on blood
pressure that is normal or only mildly elevated. Stevia has also been shown to lower
blood sugar levels in people with diabetes.
2. Erythritol: It is another low-calorie sweetener. It’s a sugar alcohol found naturally in
certain fruits. However, powdered erythritol available for purchase is most likely made
via an industrial process. It contains 0.24 calories per gram, or about 6% of the calories in
an equal amount of sugar, with 70% of the sweetness. Erythritol doesn't spike blood
sugar or insulin levels and has no effect on blood lipids like cholesterol or
triglycerides.It’s absorbed into the body from the intestine but eventually excreted from
the kidneys unchanged.

3. Glycyrrhiza glabra: Liquorice roots, which are wrinkled and brown on the outside and
yellow on the inside, contain glycyrrhizin, a compound that is 50 to 150 times as sweet as
cane sugar.
4. T h a u m a t i n : The Thaumatins are a family of very sweet proteins present in
the fruits of the tropical plant Thaumatococcus danielli (marantaceae) a bushy
plant.Thaumatin elicits a very sweet taste that is rated to be 2000 to 10000 times
sweeter than sucrose, depending on purity and concentration. Thaumatin I and II
are soluble in water and dilute alcohol. Thaumatin is effective at masking bitter
notes often associated with pharmaceuticals or vitamins.
Natural Binding agents: A binding agent (or binder) is a substance that holds or draws
other materials together mechanically, chemically or as an adhesive, to form a cohesive whole.

Pectin: Pectins are non-starch, linear polysaccharides extracted from the plant cell walls. In
the food industry, folic acid incorporated microcapsules were prepared using alginate and
combinations of alginate and pectin polymers so as to improve stability of folic acid. The
blended alginate and pectin polymer matrix increased the folic acid encapsulation efficiency and
reduced leakage from the capsules as compared to those made with alginate alone; they showed
higher folic acid retention after freeze drying and storage.

Guar gum: Guar gum comes from the endosperm of the seed of the legume plant Cyamopsis
tetragonolobus. Refined guar splits are obtained when the fine layer of fibrous material, which
forms the husk, is removed and separated from the endosperm halves by polishing. Strong acids
cause hydrolysis and loss of viscosity, and alkalies in strong concentration also tend to reduce
viscosity. It is insoluble in most hydrocarbon solvents.

Khaya gum: Khaya gum is a polysaccharide obtained from the incised trunk of the tree Khaya
grandifoliola (family Meliaceae). The fact that the gum is naturally available, inexpensive and
non-toxic has also fostered the interest in developing the gum for pharmaceutical use. Further
work has also shown its potential as a directly compressible matrix system in the
formulation of 61 controlled release tablet.

Different starches like rice, maize, corn wheat are also used a a natural binding agents. They are
added to the tablet formation to increase inter-particulate bonding strength in the tablets. The
binder is added either in dry mix or mix in granulating liquid and form matrix with fillers and
drug embedded in it.

Herbal diluents: Natural diluents include starches, hydrolyzed starches, and partially
pregelatinized starches. Common diluents include anhydrous lactose, lactose monohydrate, and
sugar alcohols such as sorbitol, xylitol and mannitol. Diluents provide better tablet properties
such as improved cohesion or to promote flow.

Classification of diluents:

Diluents are classified on the basis of chemical nature and solubility. Organic materials
Carbohydrates and modified carbohydrates are the major examples. i.e. lactose, starch and
pre‐gelatinized starch, sucrose, mannitol, sorbitol, powdered and microcrystalline cellulose.

Methyl-cellulose:
Methylcellulose is the organic material used as a diluent in the pharmaceutical formulation.
It is the cellulose derivative. On the long term use as a diluent in the pharmaceutical
formulation it causes the various side effects . Mostly it causes the abdominal fullness,
difficulty swallowing, nausea, rectal bleeding, stomach pain, and vomiting .
Dicalcium phosphate: Dicalcium phosphate (DCP) is a combination of positively charged
particles of calcium and negatively charged particles of hydrogen phosphate which is
interchangeable with the phosphate in the body. Long term use of DCP
results in upset in the balance of phosphates and other chemicals in the body. According to
the material safety data sheet, the powdered form of DCP may irritate skin. Prolonged skin
contact may lead to dry or chapped skin.

Binders: Excipients are also known as additives, which are used with active pharmaceutical
ingredients to convert in to a pharmaceutical dosage form for suitable administration. As name
indicates, Binders are the excipient which is use to bind or hold all ingredients used in
formulation of the dosage form. Binders are mixed in formulation to convey plasticity or to
increase the bonding strength between the particles in formulation. The griping of ingredients in
tablets and granules is very important which is enhanced by binders. They ensure that the
formulations are manufactured according to required physical strength and quantity. Binders are
used either in a solution or in a dry form depending on the ingredients in the formulation & the
method of preparation of dosage form. Generally, binders are used in solid or semi-solid
formulations. Examples of dosage form in which binders are used are as follow: Tablets, Pills,
Pallets, Granules, and Pastes etc.

Viscosity builders: These are substances, which added to mixture, to increase its viscosity
without substantially modifying its other properties, such as taste.They increase stability. It is
desirable to increase the viscosity of dosage form to provide or to improve palatability or
pourability.

Flavoring agents: Flavors are the mixed sensation of taste, touch, smell & sight. Nowadays,
many artificial flavors are manufactured with the help of technology in flavoring industries.
Many pharmaceutical industries use flavors in many formulations like: cough syrups, sedatives,
anti-malarial and anti-biotic. Flavors are used as taste masking agents which hides the unpleasant
taste or order of dosage form. A flavor enhances the likelihood of medicine and makes them
more compatible for patient’s administration. Due to the use of flavors in dosage form children
take medicines without any problem. Flavoring agents may be artificial or natural. Artificial
flavoring agents are synthesized in laboratories while natural flavoring agents are extracted from
plants.Sweetening agents also separated from plants and also manufactured synthetically.
Examples of dosage form in which flavoring agents are used are as follow: Tablets, Pills, Pallets,
Capsules, Pastes, Syrups, Emulsions, Suspensions, Mouth washes etc. Examples of flavoring
agents are Black pepper, Cardamom, Fennel, Ginger, Peppermint, Nutmeg and saffron.

Coloring agents: Coloring agents comes under the category of organoleptic agents. Coloring
agents are widely used in pharmaceuticals, cosmetics and food industries. Coloring agents
promotes the appearance in pharmaceutical formulations. If any dosage form has unacceptable
color, the consumers avoid the dosage form for administration. Coloring agents give the
attractiveness to the dosage form. Coloring agents are also used for differentiate of dosage form
or for easy identification of dosage forms. Due to the use of coloring agents in dosage forms
psychologically patients are attracted towards the dosage forms. Coloring agents are also used as
dyes and widely used in cosmetics industries. All coloring agents used in pharmaceutical
industries is approved or certified by FDA. Example of dosage forms in which coloring agents
are used:- Tablets, Pills, Pallets, Capsules, Pastes, Ointments, Syrups, Emulsions, Suspensions
etc.

Perfumery agents: An active ingredient is a compound which imparts the aroma to the perfume
compositions or enhances the aroma of an existing perfume compostion. Perfumary agents includes
Musk, sandalwood oil, Rose oil, Jasmine oil, benzoin, Turpentine and Levender oil.

Herbal Formulations
Herbal formulations means a dosage form consisting of one or more herbs or processed herbs in
specified quantities to provide specific nutritional, cosmetic benefits meant for use to diagnose,
treat, mitigate diseases of human beings or animals, alter the structure or physiology of human
beings or animals.

Herbal syrup: Syrup is a concentrated mixture of sugar in purified water. The oral use of liquid
pharmaceutical has generally been justified on the basis of ease of administration to those
individuals who have difficulties in swallowing solid dosage forms. Ayurvedic herbal cough
syrup comprising goodness of herbs such as Tulsi, Liquorice, Ginger, Vasaka which has been
reported to provide effective relief in cough without causing adverse effects like those associated
with the use of antihistamines. Combination of these herbs with honey is intended to provide
additive benefit in relieving symptoms of acute non-productive cough.

Preparation of Herbal Syrup: An herbal syrup is prepared by combining a concentrated

decoction with either honey or sugar, and sometimes alcohol. The base of such a syrup is a
strong herbal decoction. Mixing a decoction with honey or sugar helps to thicken and preserve
the decoction. This increases the shelf life of the decoction and often creates a soothing
application that benefits situations such as sore throat, cough, dry irritated tissues, and digestive
issues. The added sweetener can also help to increase the palatability of some herbs. Many folks,
including children, find syrups to be delicious. The basic proportions you want to use are 2 parts
herbal decoction to 1 part honey or sugar. This is called a 2:1 ratio. This means that if you start
with your herbs added to 4 cups of water and simmer down the liquid to 2 cups of decoction,
then you will want to add 1 cup of honey or sugar to create and adequately preserve your syrup.
Some herbalists like to use a 1:1 ratio of decoction to honey/sugar while others find a 1:1 ratio to
result in a syrup that is too sweet. The increased amount of honey/sugar relative to decoction in a
1:1 ratio will be better preserved and hence last longer.
Herbal Tablets: Tablets may be defined as the solid unit dosage form of medicament or
medicaments with suitable excipients and prepared either by molding or by compression. It
comprises a mixture of active substances and excipients usually in powder form, pressed or
compacted from a powder into a solid dose. The excipients can include diluents, binders, glidants
and lubricants to ensure efficient tableting. Disintegrants to promote tablet break-up in the
digestive tract; sweeteners or flavours to enhance taste; and pigments to make the tablets visually
attractive or aid in visual identification of an unknown tablet. A polymer coating is often applied
to make the tablet smoother and easier to swallow, to control the release rate of the active
ingredient, to make it more resistant to the environment (extending its shelf life), or to enhance
the tablet's appearance.

Tablet Evaluation:

Before a tablet is released out into the market it has to pass a few quality checks, which is
mandatory. Evaluation of tablet includes the assessment of tablets physical, chemical and
biological properties. To studies them the following test are formulated:

• Appearance

• Size and Shape,

• Organoleptic properties,

• Uniformity of thickness,

• Hardness,

• Friability,

• Determination of pH

• Specific gravity

• Stability testing

Novel drug delivery system:

“Novel Drug delivery System (NDDS) refers to the formulations, systems and technologies for
transporting a pharmaceutical compound in the body as it is needed to safely achieve its
desired therapeutic effects. Drug delivery systems (DDS), are based on approaches that are
interdisciplinary and that combine pharmaceutics, bio conjugate chemistry, and molecular
biology.It is a novel approach to drug delivery that addresses the limitations of the traditional
drug delivery systems. Our country has a vast knowledge base of ayurveda whose potential is
only deing realized in the recent years.
The therapeutic benefits of these new systems include: Increased efficacy of the drug, Site
specific delivery, and decreased toxicity/side effects, increased convenience, viable treatments
for previously incurable diseases, Potential for prophylactic application, Better patient
compliance.

PHYTOSOMES
Phytosomes are also known as herbosomes, are recently added herbal formulations that are better
absorbed than extracts. Phytosomes are prepared through the attachment of individual
ingredients of herbal extracts to phosphatidyl-choline, resulting in a formulation having higher
solubility and hence better absorption leading to promoted pharmacokinetic and
pharmacodynamic properties compared to the conventional herbal extracts. Various popular
herbal extracts including Ginkgo biloba, grape seed, hawthorn, green tea, and ginseng have been
incorporated in phytosomes. The active components of these herbal extracts were successfully
bound to phosphatidyl choline. Phytosomes, also known as phospholipid complexes, are well-
known delivery systems that are closely related to liposomes in terms of their structure and
configuration. Phytosomes have a higher capacity for nutraceutical compounds to be added to
them, as they have a quite stable, chemically bound structure. Plant extracts can bind quite easily
to phosphatidylcholines due to the presence of terpenoids and flavonoids. As delivery systems,
phytosomes have proved to be superior to liposomes. The chemical bonding ensures the stability
of phytosomes, enhances the encapsulation efficiency and stability of bioactives, generally at a
stoichiometric molar ratio of 1:1 or 1:2 (phospholipids: phytochemicals) Phytosomes were found
to improve solubility, permeability rate and bioavailability of active compounds in various cases
and inhibit or delay physical and chemical degradation and could be implemented without
generating any toxic effects. The choline head of the phosphatidylcholine molecule binds to
these compounds while the fat-soluble phosphatidyl portion comprising the body and tail
envelops the choline-bound material. The phytosome process also intensifies the action of herbal
compounds by improving absorption, increasing biological activity, and enhancing delivery to
the target tissue.
Methods of Preparation: For the preparation of Phytosomes the phytoconstituents like
bioflavonoids, flavolignan and polyphenolic compounds reacting drop by drop by the
solution of natural or synthetic phospholipids like Phosphatidycholine with vigorous stirring.
Phytosomes of ginsenoside, puerarin and kushenin are prepared in this manner. Another
example is the Curcumin phospholipids complexes which can be prepared when the ethanol
solution of the hydro-alcoholic extract of turmeric rhizomes adding the phospholipids,
under reflux and with stirring. Phytosomes which are prepared by the non solvent, freeze
drying, spray drying or vacuum drying are called the prepared complex phytosome.

ADVANTAGES OF PHYTOSOMES

1. Improve the absorption of lipid insoluble polar phytoconstituents, enhance the bioavailability.

2. Appreciable drug entrapment which becomes very beneficial.

3. Reduce the dose due to increased absorption.

4. Phosphatidylcholine shows synergistic effect because it is a hepatoprotactive also.

5. Phytosomes are more stable because of the chemical bonding between the
phytoconstituents and carrier i.e. phophatidylcholine.

6. Effective in cosmetics.
 Semester- 6th
Subject: Herbal Drug Technology

Subject code: BP603

Module - 4

Evaluation of Herbal Drugs

Objectives: upon compilation of this module the student should be able to:

1. Understand WHO and ICH guidelines for assessment of herbal drugs

2. Know the Stability testing of herbal drugs
3. Patenting aspects of traditional knowledge and natural products
4. Know about the various Regulatory issues in India

Learning outcomes: the student will be able to:

1. Learn the WHO guidelines for evaluation of herbal drugs.

2. Learn about the methods for stability testing of herbal drugs
3. Learn about the patent, IPR, Farmers Right, Bioprospecting and Biopiracy
4. Learn about the Regulation of manufacture of ASU drugs, Cosmetic Act and Schedule Z
drugs.

Introduction: The safety and efficacy of herbal drugs remain major issues of concern especially
in the developing world where the use is high. The evaluation of herbal drugs involves
confirmation of its identity, quality, purity and detection of nature of adulteration. Thus, the
evaluation parameters are based upon chemical, physical, microbiological, therapeutic and
toxicological studies. It also serves as an important tool in stability studies.

WHO guidelines:
The WHO guidelines present general consideration on potentially hazardous contaminants and
residues in herbal medicines. It includes guiding principles of assessing quality of herbal
medicines in terms of major contaminants and residues. It also recommends analytical methods
for qualitative and quantitative determination of such contaminants and residues. The objectives
of these guidelines are to provide:

a. Quality control of crude drugs material, plant preparations and finished products.

b. Stability assessment and shelf life.

c. Safety assessment; documentation of safety based on experience or toxicological studies.

d. Assessment of efficacy by ethno-medical informations and biological activity evaluations.

The scope of these guidelines does not cover issues of adulteration of herbal medicines. It
should be noted that these methods need to be validated for the material that is to be tested and
also for each type of instruments. The other WHO documents and publications relating to the
quality assurance of herbal medicines with regard to safety should include the following steps:

1. Authentication (Stage of collection, parts of the plant collected, regional status, botanical
identity like phytomorphology, microscopical and histological analysis, taxonomical identity,
etc.)

2. Foreign matter (herbs collected should be free from soil, insect parts or animal excreta, etc.)

3. Organoleptic evaluation (sensory characters – taste, appearance, odor, feel of the drug, etc.)

4. Tissues of diagnostic importance present in the drug powder.

5. Ash values and extractive values.

6. Volatile matter

7. Moisture content determination

8. Chromatographic and spectroscopic evaluation. TLC, HPTLC, HPLC methods will provide
qualitative and semi quantitative information about the main active constituents present in the
crude drug as chemical markers in the TLC fingerprint evaluation of herbals (FEH). The quality
of the drug can also be assessed on the basis of the chromatographic fingerprint.

9. Determination of heavy metals – e.g. cadmium, lead, arsenic, etc.

10. Pesticide residue – WHO and FAO (Food and Agricultural Organization) set limits of
pesticides, which are usually present in the herbs. These pesticides are mixed with the herbs
during the time of cultivation. Mainly pesticides like DDT, BHC, toxaphene, aldrin cause serious
side-effects in human beings if the crude drugs are mixed with these agents.

11. Microbial contamination – usually medicinal plants containing bacteria and molds are
coming from soil and atmosphere. Analysis of the limits of E. coli and molds clearly throws light
towards the harvesting and production practices. The substance known as afflatoxins will
produce serious side-effects if consumed along with the crude drugs. Afflatoxins should be
completely removed or should not be present.

12. Radioactive contamination – Microbial growth in herbals are usually avoided by irradiation.
This process may sterilize the plant material but the radioactivity hazard should be taken into
account. The radioactivity of the plant samples should be checked accordingly to the guidelines
of International Atomic Energy (IAE) in Vienna and that of WHO.
The quality of the raw materials can be tested according to the following format:

• Name of the drug (English, Regional names, Exact botanical nomenclature)

• Part of the plant used
• Area of collection
• Distribution details
• Season of Crop
• Time and year of collection
• Pesticide and insecticides
• Condition of the drug (fresh or dry)
• Form of the drug (powdered or intact or cuttings like etc.

In order to obtain quality oriented herbal products care should be taken right from the proper
identification of plants; season and area of collection, extraction, isolation and verification
process. Chemical and instrumental analyses are routinely used for analyzing synthetic drugs to
confirm its authenticity. In the case of herbal drugs, however the scene is different especially for
polyherbal formulation, as there is no chemical or analytical methods available. The herbal
formulations in general can be standardized schematically as to formulate the medicament using
raw materials collected from different localities and a comparative chemical efficacy of different
batches of formulation are to be observed. The preparation with better clinical efficacy are to be
selected. After all the routine physical, chemical and pharmacological parameters are to be
checked for all the batches to select the final finished product and to validate the whole
manufacturing process.
Stability testing of herbal drugs: It is a challenging risk, because the entire herb or herbal
product is regarded as the active matter, regardless of whether constituents with defined
therapeutic activity are known. The most important aspect in the evaluation of the stability study
of a product and its storage condition. The purpose of a stability testing is to provide proof on
how the quality of the herbal products varies with the time under the influence of environmental
factors such as temperature, light, oxygen, moisture, other ingredient or excipients in the dosage
form, particle size of drug, microbial contamination, trace metal etc.

Stability studies should be performed on at least three production batches of the herbal products
for the proposed shelf-life, which is normally denoted as long term stability and is performed
under natural atmospheric conditions.With the help of modern analytical techniques like
spectrophotometry, HPLC, HPTLC and by employing proper guidelines it is possible to generate
a sound stability data of herbal products and predict their shelf-life, which will help in improving
global acceptability of herbal products.

Shelf-life

The determination of shelf life of herbal medicinal drug products is same as chemically defined
APIs, but special nature of herbal product should be taken into consideration. It is recommended
that in case of a herbal medicinal product containing a natural product or a herbal drug
preparation with constituents of known therapeutic activity, the variation in component during
the proposed shelf-life should not exceed ± 5% [5,6]of the initial assay value, unless justified to
widen the range up to ±10 per cent or even higher. The low marker concentration in the finished
product, justify the wider range. Additionally, due to the influences of climate, harvesting and
biological variance, the natural variation of the marker content needs to be taken into account.
For example, the linearity of the method may be tested over a range of 40-160 per cent of the
marker’s expected content in the extract and/or product. During stability testing, a setting up of
the limits to ±10 per cent is accepted for the finished product, by the justification of matrix
effects (placebo), the lack of precision and selectivity (combination products) and the low
analyte concentrations. Considering that the marker content cannot be defined to a specified
level, the relative changes from the starting value are specified (95-105 per cent or 90-110 per
cent ‘from the initial value).

Challenges in Stability testing of herbal medicinal product:

1. Active substances (herbal substances and/or herbal preparations) in HMPs consist of

complex mixtures of constituents and in most cases the constituents responsible for the
therapeutic effects are unknown.
2. The situation is further complicated when two or more herbal substances and/or herbal
preparations are combined in a Herbal formulations.
3. In addition, many herbal substances/herbal preparations are known to be unstable.
Taking into account these special features of Herbal Medicinal Products, adequate quality
concepts have been established. As part of a total control strategy for herbal substances, herbal
preparations and Herbal Medicinal Products, a set of test criteria including qualitative and
quantitative parameters has been recognized as quality indicating. With regard to stability tests,
chromatographic fingerprints as well as appropriate methods of assay via marker substances
represent the fundamental part of this concept, laid down in shelf-life specifications.
Notwithstanding the appropriateness of this approach, its realization is often associated with
analytical problems and high costs.

Mechanisms involved in change product: Loss of activity, Change in concentration of active

component, Alteration in bioavailability, Loss of content uniformity, Loss of elegance,
Formation of toxic degradation product, Loss of packaging integrity.
Importance of Stability testing: It evaluates the efficacy of a drug. Stability studies are used to
develop suitable packaging information for quality, strength, purity & integrity of product during
its shelf life. It is used for determination of the shelf life.

Stress testing: Stress testing help to identify the degradation product, which can help to establish
the degradation pathway. Stress tests are usually considered unnecessary for herbal drug & its
preparation.

1. For herbal drugs and herbal drug preparations, a testing under accelerated or
intermediate conditions may be omitted. This should apply to finished products as
well, because it is known that most products fail at 30°C/65 per cent relative humidity
(RH) and at 40°C/75 per cent RH in particular. Herbal drug substances at only
25°C/60 per cent RH, with no requirement for intermediate/ accelerated testing.
2. If intermediate conditions are tested, the three-month time-point is omitted (that is, 0,
6, 9 and 12 months). In some cases of combination products, it is hardly possible to
provide the required two batches of each extract at the same time due to different
harvesting times.

Selection of batches: Long term testing is to be provided with on at least two batches of the drug
substance and three batches of drug product. In some cases of combination products, it is hardly
possible to provide the required two batches of each extract at the same time due to different
harvesting times. This should be taken into consideration when planning the schedule for
stability study.

Predictable changes in Herbal medicinal Product: Following predictable changes may

occurs in herbal medicinal product during storage and in shelf life determination: Hydrolysis,
Oxidation, Racemization, Geometric isomerization, Temperature, Moisture and Light

Hydrolysis: Reaction with water takes place results in degradation of product.

Oxidation: Due to addition of electro negative atom, Removal of electro positive atom,
radicals formation results in decomposition of natural products.

Racemization: Racemization is the process in which one enantiomer of a compound, such as an

L-amino acid, converts to the other enantiomer. The compound then alternates between each
form while the ratio between the (+) and (–) groups approaches 1:1, at which point it becomes
optically inactive.

Geometric isomerization: Products can be change in trans or cis form. One form may be more
therapeutically active.

Polymerization: There is combination of two or more identical molecule to form much larger &
more complex molecule.
Temperature: The rate of most chemical increase with increase in temperature. So that
“Tropical” area must be taken in consideration during preparation of the formula of the herbal
substance.

Moisture: Moisture absorbed on to the surface of solid drug will often increase the rate of
decomposition, if it is susceptible to the hydrolysis.

Light: Many type of chemical reaction induced by exposure to light of high energy.
Autoxidation of volatile oil / fixed oil takes place and substance becomes colored.

Patenting and Regulatory requirements of natural products

Patent: A patent is a monopoly right, which is granted to a patentee for a limited period of time
during which he is given the exclusive right to hinder anyone else from using her invention
without consent. Thus it is a negative right as it doesn’t grant anyone the right to produce or do
anything, simply the right to hinder others from doing or producing what is covered by the
patent. Patents as a legal institution have evolved over hundreds of years. The scope, length and
purpose for protection has changed many times and it is of value to this paper to examine the
developments in relation to the developments occurring in the Southern countries but at a much
more accelerated pace as a means of mirroring the development. A patent can be granted for an
invention which may be related to any process or product. The word “Invention “has been
defined under the Patents Act 1970 as amended from time to time. “An invention means a new
product or process involving an inventive step and capable of industrial application. A patent
gives its owner the right to exclude other from making,using,selling and importing an invention
for a limited period of time, usually 20 years. The patent rights are granted in exchange for an
enabling public disclosure of the invention.
Intellectual property rights (IPRs): These are rights to make, use, and sell a new product or
technology that are granted, usually for a period of 17- 20 years, solely to the inventor or the
corporation which files a claim on the inventor's behalf. IPRs are meant to reward innovators,
inventors and researchers. It is a driving force behind rapid industrial growth and progress.
Under intellectual property law, owners are granted certain exclusive rights to a variety of
intangible assets, such as musical, literary, and artistic works, discoveries and inventions, words,
phrases, symbols, and designs. Common types of intellectual property include copyrights,
trademarks, patents, industrial design rights and trade secrets in some jurisdictions. Among
various kinds of IPRs patents and trademarks are more important to pharmaceutical industries.
IPR does not provide protection for inventions that are based on prior existing knowledge.
A patent is a set of exclusive rights granted by a state (national government) to an inventor or
their assignee for a limited period of time in exchange for a public disclosure of an invention.The
association of patents and thievery has a long history. When Columbus sailed out to "discover" a
world that was new to him, he was carrying letters patent from the King and Queen of Spain. The
procedure for granting patents, the requirements placed on the patentee, and the extent of the
exclusive rights vary widely between countries according to national laws and international
agreements. Typically, however, a patent application must include one or more claims defining
the invention which must be new, inventive, and useful or applicable. In most countries, both
natural persons and corporate entities may apply for a patent. The grant and enforcement of
patents are governed by national laws, and also by international treaties.
Pharmaceutical companies have been making use of traditional knowledge of tribal people to
identify plants and their ingredients for developing new medicines. Researchers, screening plants
for useful substances can cut down time taken, by getting information from tribal healers on
variety of plants used for treating ailments. Many pharmaceutical corporations are misusing
traditional knowledge and making huge profits in form of what is known as biopiracy. Trade
secret is an IPR which provides simplified protection. It does not require registration with
government and is not bound by time. It is useful in countries like India in managing heavy cost
of IP protection.
Farmers Rights: Farmers may have little or no understanding of the scientific basis of genetic
diversity, but they certainly understand its paramount importance to agriculture, and the need for
promoting variability in agricultural practices. The autonomy that every farmer exercises in
selecting, saving and maintaining seed for re-sowing has been fundamental for the agronomic
transformation of plant species into crops, and their further selection.
Farmers’ rights and intellectual property rights: The basic principle underlying IPR on plant
varieties is the recognition of human innovation in developing a new plant variety through
selection, with or without recombination, which is novel and distinct from the pre-existing
varieties. Unlike the innovations that are made in many non-biological domains, life forms such
as crop varieties are not completely invented, but are always created from pre-existing life forms
and propagated by natural processes. Thus, the creation of a new variety has two components:
the use of pre-existing varieties and the knowledge required to select a new variety by
recombining the pre-existing ones or by other processes. Equity demands that the recognition of
innovations made on the newly bred varieties should also include the similarly innovative
component invested in the source varieties (i.e. plant genetic resources). The latter essentially
represent the far greater cumulative intellectual inputs contributed by generations of farming
communities over a long period. The fact that those communities lack identity and institutional
backing, unlike the present commercial plant breeders, should not mean that they are given less
importance or recognition for their intellectual inputs. While IPR on plant varieties are upheld,
the demand for free access to varieties developed by farmers, without the payment of royalties
applicable to varieties protected by intellectual property (IP), can be seen as a double standard
concerning rights. Moreover, the granting of exclusive rights over the seed or propagating
material of an IP-protected variety marks a turning point from the traditional unrestricted right
farmers had enjoyed over seed. This restriction on the seed of a patent-protected variety is
rigorous, allowing no flexibility for farmers and minimal flexibility for breeders, depending on
the jurisdiction.
Plant breeders Rights (PBR): These are also known as plant variety rights (PVR). These are
the rights granted to the breeder of a new variety of plant that give the breeder exclusive control
over the propagating material and harvested material of a new variety for a number of years.
With these rights, the breeder can choose to become the exclusive rights, a variety must be new,
distinct, uniform and stable. PBRs allow a plant breeder to exclude others from the production,
processing, stocking, distribution, marketing, sale, export and import of propagating material of a
protected variety for a specified number of years. It also allows the breeder to license such rights
to others, and to receive royalties generated from the authorized use of the propagating material.
These rights may in some countries also include harvested material, such as cut flowers, fruits or
foliage of the protected variety, in cases where the breeders do not have reasonable opportunities
to exercise their rights over the planting materials. The legal space available to farmers
concerning the seed of a protected variety under such a system for plant varietal protection takes
the form of farmers’ rights, together with PBRs; or that of the farmers’ privilege within PBRs.

Biopiracy: When researchers use traditional knowledge without permission, or exploits the
cultures they’re drawing from – it’s called biopiracy. Biopiracy happens when researchers or
research organisations take biological resources without official sanction, largely from less
affluent countries or marginalised people. Biopiracy is not limited to drug development. It also
occurs in agricultural and industrial contexts. Indian products such as the neem tree, tamarind,
turmeric, and Darjeeling tea have all been patented by foreign firms for different lucrative
purposes.

The term biopiracy was coined by Pat Mooney, to describe a practice in which indigenous
knowledge of nature, originating with indigenous peoples, is used by others for profit, without
authorization or compensation to the indigenous people themselves. For example, when
bioprospectors draw on indigenous knowledge of medicinal plants which is later patented by
medical companies without recognizing the fact that the knowledge is not new or invented by the
patenter, this deprives the indigenous community of their potential rights to the commercial
product derived from the technology that they themselves had developed. Critics of this practice,
such as Greenpeace, claim these practices contribute to inequality between developing countries
rich in biodiversity, and developed countries hosting biotech firms. In the 1990s many large
pharmaceutical and drug discovery companies responded to charges of biopiracy by ceasing
work on natural products, turning to combinatorial chemistry to develop novel compounds.

Bioprospecting: It is the process of discovery and commercialization of new products based

onbiological resources. Despite indigenous knowledge being intuitively helpful, bioprospecting
has only recently begun to incorporate such knowledge in focusing screening efforts for
bioactive compounds. During 1981-2010, one third of all small molecule new chemical entities
approved by the U.S. Food and Drug Administration (FDA) were either natural products or
compounds derived from natural products. Despite indigenous knowledge being intuitively
helpful, bioprospecting has only recently begun to incorporate such knowledge in focusing
screening efforts for bioactive compounds. Bioprospecting may involve biopiracy, the
exploitative appropriation of indigenous forms of knowledge by commercial actors, and can
include the patenting of already widely used natural resources, such as plant varieties, by
commercial entities.
Traditional knowledge (TK): The concept of traditional knowledge is too varied to have
a single definition as such a definition would be prejudicial to the various forms of knowledge
that are held by traditional communities. No superficial legal definition will sufficiently
encompass the complex social and legal systems that sustain traditional knowledge within the
original communities. Nonetheless it is very necessary to arrive at certain demarcating standards
defining traditional knowledge if such knowledge is to be protected. The most practical method
of protection is the prevention of unauthorized use by third parties beyond the traditional circle.
This form of protection focuses on the use of any indigenous knowledge as technical, ecological,
scientific, medical or cultural by a traditional community. A report by WHO says that about 80%
of World’s population is depending on the traditional knowledge on the ancient methods for
curing disease. The traditional knowledge is based on indispensable for its primary health care
uses. For example, the Neem and its uses can be registered under traditional knowledge by
indigenous people of India for its medical uses which includes first aid, cosmetic nature and for
curing inflammation and redness caused by any medical issue. This is based on herbal plant used
for medical purpose and it is called “arogyapaacha”.

“Traditional knowledge refers to the knowledge, innovations and practices of indigenous and
local communities around the world. Developed from experience gained over the centuries and
adapted to the local culture and environment, traditional knowledge is transmitted orally from
generation to generation. It tends to be collectively owned and takes the form of stories, songs,
folklore, proverbs, cultural values, beliefs, rituals, community laws, local language, and
agricultural practices, including the development of plant species and animal breeds. Traditional
knowledge is mainly of a practical nature, particularly in such fields as agriculture, fisheries,
health, horticulture, forestry and environmental management in general.
Case study of Neem: The Neem tree (Azadirachta Indica) is a large tropical evergreen that
can grow up to 30 meters tall and 2.5 meters in girth. The tree carries a yellow or greenish
yellow fruit, which holds a seed. The exact origin of the tree is unknown, it is found in many
different countries but it is in India that the tree is most widely spread; the subcontinent is
estimated to contain approximately 18 million Neem trees. The tree has been shown to be useful
in many different areas including contraception, dental hygiene and pesticides, as well as being
part of many traditional Indian medicines and cures. The widespread growth of the Neem tree
and its many practical uses has made the Neem tree very dear to the Indian people to whom it
represents an integral part of their traditional and even religious heritage. Indian scientists have
been researching the Neem tree as a natural pesticide since the 1920’s but Western awareness of
its qualities wasn’t raised until 1959 when German entomologist Heinrich Schmutterer witnessed
a locust plague in the Sudan and noticed that the Neem trees were the only ones that had
withstood the onslaught. He immediately started studying the Neem tree and his work in turn
generated a great deal of western scientific interest in its pesticidal qualities.That the Neem tree
could withstand locust infestations had been common knowledge among Indian farmers for
centuries. Both the seeds and to a lesser extent the leaves contain the active substance
azadirachtin, which is a powerful insecticide that is not harmful to human beings. Even before
the discovery of the active substance in the later half of the 20th century, Neem seeds had been
used by Indian farmers as a natural pesticide. The most common practice was to break up the
seeds, soak them in water or alcohol, and then apply the resulting emulsion on their crops. The
efficiency of this practice was however limited by the rapid degradation of the chemical solution
which usually only lasted a couple of days. The first U.S. patent on a storage stable composition
for Neem seed extract was issued in 1985 to inventor Robert O. Larsson.. W.R. Grace in
partnership with The United States of America as represented by The Secretary of Agriculture
jointly filed a Patent Application for the formulation with the EPO, who after a long drawn out
examination process granted the applicants the patent in 1994. The main claim of the patent had
however been restricted by the EPO in relation to the patent granted in the U.S. The aim of the
opponents was to revoke the patent, and more specifically on the grounds of prior use and TK so
as to gain an important case law precedent in their battle against biopiracy. The decision of the
opposition division followed along the lines of what they were after. The claim was rejected on
the grounds of lacking novelty and the evidence upon which this decision was taken was the
testimony of a witness who had worked with the process himself and who could verify its use
among Indian farmers. The decision of the Board of appeal to leave open whether prior art had
been proven or not changed the whole focus of the case. In choosing the article as the closest
prior art they relied on a scientific study published in a Western journal. Thereby the question of
novelty and inventive step wasn’t truly judged on the grounds of TK. The decision was taken on
the basis of comparing two scientific documents, the lack of inventive step wasn’t judged against
Indian traditional practices but the scientific studies of two scholars. The board shied away from
dealing with the issue of prior use and decided the case on materials with which they were more
comfortable. Another interesting aspect of the change is that the patentees who had declined an
oral hearing provided no defence against the article on the grounds of inventive step and only a
fleeting remark regarding the article in relation to novelty. Even if the significance of the
inadequate defence presented by the patentees is hard to discern, it cannot be ignored as a
potential factor in the decision.
Case study of Turmeric: Turmeric is a tropical herb grown in east India. Turmeric powder
is widely used in India as a medicine, a food ingredient and a dye to name a few of its uses3. For
instance, it is used as a blood purifier, in treating the common cold, and as an anti-parasitic for
many skin infections. It is also used as an essential ingredient in cooking many Indian dishes. In
1995, the United States awarded patent on turmeric to University of Mississippi medical center
for wound healing property. The claimed subject matter was the use of "turmeric powder and its
administration", both oral as well as topical, for wound healing. An exclusive right has been
granted to sell and distribute. The Indian Council for Scientific and Industrial Research (CSIR)
had objected to the patent granted and provided documented evidences of the prior art to
USPTO. Though it was a well known fact that the use of turmeric was known in every household
since ages in India, it was a herculean task to find published information on the use of turmeric
powder through oral as well as topical route for wound healing. Due to extensive researches, 32
references were located in different languages namely Sanskrit, Urdu and Hindi. Therefore,
theUSPTO revoked the patent, stating that the claims made in the patent were obvious and
anticipated, and agreeing that the use of turmeric was an old art of healing wounds. Therefore,
the TK that belonged to India was safeguarded in Turmeric case.
Regulatory Issues in India
Herbal Drug Regulation in India: Drug regulation is a public policy response to the demands
of public health and the changing needs of pharmaceutical industry. Thus, the objective of
regulatory control is a question of achieving a ‘balance’ between protecting and promoting
public health and facilitating the industry vis-à-vis compliance with regulatory standards.
Consequently, although the regulatory objectives seem clear, the actual quantum of regulatory
oversight, the mechanism for achieving regulatory compliance and the actions needed to deal
with non-compliance have to be designed in a manner that is sensitive to the characteristics of
the regulatory space,and specifically, the actors operating in that space. This is the basic premise
in the conceptual approach proposed by ‘Smart or Responsive Regulation’. The rationale behind
this is to design a regulatory system where the choice of regulatory instruments not only match
the imperatives/objectives of regulation, but also take into consideration the range and the
intrinsic characteristics of each of the regulatory stakeholders. Provision related to the
manufacture and control of Ayurvedic, Sidha and Unani (ASU) drugs has been prescribed in the
Drugs and cosmetics acts 1940. This act described the formation of drug Technical Advisory
Board (DTAB), which consist of various nominated members and Drug Consultative committees
(DCC). DTAB is the highest constitutional decision making body on technical matters related to
the drugs in the country. It is a part of central drug Standard Contro Organisation (CDSCO) in
the ministry of Health and family welfare. The drug and cosmetic act provides the establishment
of following agencies:

1. Advisory
2. Analytical
3. Executive
Drugs and cosmetics Act 1940: The Drugs and Cosmetics Act, 1940 is an Act of the
Parliament of India which regulates the import, manufacture and distribution of drugs in
India. The primary objective of the act is to ensure that the drugs and cosmetics sold in
India are safe, effective and conform to state quality standards.The related Drugs and
Cosmetics Rules, 1945 contains provisions for classification of drugs under given
schedules and there are guidelines for the storage, sale, display and prescription of each
schedule. The term "drug" as defined in the act includes a wide variety of substance,
diagnostic and medical devices. The act defines "cosmetic" as any product that is meant
to be applied to the human body for the purpose of beautifying or cleansing. The
definition however excludes soaps. In 1964, the act was amended to include Ayurveda
and Unani drugs.

Provisions related to Ayurveda, Siddha and Unani drugs (ASU):

• The Drugs Technical Advisory Board (DTAB)
• The central Drugs laboratory (CDL)
• The Drugs consultative committee (DCC)

The Drugs Technical Advisory Board (DTAB): (1) The Central Government shall, as
soon as may be, constitute a Board (to be called the Drugs Technical Advisory Board) to
advise the Central Government and the State Governments on technical matters arising
out of the administration of this Act and to carry out the other functions assigned to it by
this Act.
(2) The Board shall consist of the following members, namely:—
(i) the Director General of Health Services, ex officio, who shall be the Chairman;
(ii) the Drugs Controller, India, ex officio;
(iii) the Director of the Central Drugs Laboratory, Calcutta, ex officio;
(iv) the Director of the Central Research Institute, Kasauli, ex officio;
(v) the Director of the Indian Veterinary Research Institute, Izatnagar, ex officio;
(vi) the President of the Medical Council of India, ex officio;
(vii) the President of the Pharmacy Council of India, ex officio;
(viii) the Director of the Central Drug Research Institute, Lucknow, ex officio;
(ix) two persons to be nominated by the Central Government from among persons
who are in charge of drugs control in the States;
(x) one person, to be elected by the Executive Committee of the Pharmacy Council of
India, from among teachers in pharmacy or pharmaceutical chemistry or pharmacognosy
on the staff of an Indian university or a college affiliated thereto;
(xi) one person, to be elected by the Executive Committee of the Medical Council of
India, from among teachers in medicine or therapeutics on the staff of an Indian
university or a college affiliated there to.

The Central Drugs Laboratory (CDL): The Central Government shall, as soon as may
be, establish a Central Drugs Laboratory under the control of a Director to be appointed
by the Central Government, to carry out the functions entrusted to it by this Act or any
rules made under this Chapter.

The Drugs Consultative Committee (DCC): The Central Government may constitute
an advisory committee to be called “the Drugs Consultative Committee” to advise the
Central Government, the State Governments and the Drugs Technical Advisory Board on
any matter ending to secure uniformity throughout [India] in the administration of this
Act. The Drugs Consultative Committee shall consist of two representatives of the
Central Government to be nominated by that Government and one representative of each
State Government to be nominated by the State Government concerned. The Drugs
Consultative Committee shall meet when required to do so by the Central Government
and shall have power to regulate its own procedure.

Manufacture for sale of Ayurvedic, Siddha and Unani drugs:

(1) The Central Government shall, by notification in the Official Gazette and with effect
from such date as may be specified therein, constitute a Board (to be called
the[Ayurvedic, Siddha and Unani Drugs Technical Advisory Board]) to advise the
Central Government and the State Governments on Technical matters arising out of
this Chapter and to carry out the other functions assigned to it by this Chapter.

(2) The Board shall consist of the following members, namely:

(i) the Director General of Health Services ex officio;

(ii) the Drugs Controller, India, ex officio;

(iii) the principal officer dealing with Indian systems of medicine in the Ministry of
Health, ex officio];

(iv) the Director of the Central Drugs Laboratory, Calcutta ex officio;

(v) one person holding the appointment of Government Analyst under section 33F, to be
nominated by the Central Government;

(vi) one Pharmacognocist to be nominated by the Central Government;

(vii) one Phyto-chemist to be nominated by the Central Government;

(3) The Central Government shall appoint a member of the Board as its Chairman.
(4) The nominated members of the Board shall hold office for three years but shall be
eligible for renomination.

(5) The Board may, subject to the previous approval of the Central Government, make
bye -laws fixing a quorum and regulating its own procedure and conduct of all business
to be tran -sacted by it.

(6) The functions of the Board may be exercised notwithstanding any vacancy therein.

(7) The Central Government shall appoint a person to be Secretary of the Board and
shall provide the Board with such clerical and other staff as the Central Government
considers necessary.

The Ayurvedic, Siddha and Unani Drugs Consultative Committee: (ASU)

1) The Central Government may constitute an Advisory Committee to be called the
Ayurvedic, Siddha and Unani Drugs Consultative Committee to advise the Central
Government, the State Governments and the Ayurvedic, Siddha and Unani Drugs
Technical Advisory Board on any matter for the purpose of securing uniformity
throughout India in the administration of this Act in so far as it relates to Ayurvedic,
Siddha or Unani drugs.

(2) The Ayurvedic, Siddha and Unani Drugs Consultative Committee shall consist of two
persons to be nominated by the Central Government as representatives of that
Government and not more than one representative of each State to be nominated by the
State Government concerned.
(3) The Ayurvedic, Siddha and Unani Drugs Consultative Committee shall meet when
required to do so by the Central Government and shall regulate its own procedure.

Prohibition of manufacture and sale of certain Ayurvedic, Siddha and Unani

Drugs: From such date as the State Government may, by notification in the Official
Gazette, specify in this behalf, no person, either by himself or by any other person on his
behalf, shall—
(a) manufacture for sale or for distribution—
(i) any misbranded, adulterated or spurious Ayurvedic, Siddha or Unani drug;
(ii) any patent or proprietary medicine, unless there is displayed in the prescribed
manner on the label or container thereof the true list of all the ingredients contained in it;
(iii) any Ayurvedic, Siddha or Unani drug in contravention of any of the provisions of
this Chapter or any rule made there under;
(b) sell, stock or exhibit or offer for sale or distribute any Ayurvedic, Siddha or Unani
drug which has been manufactured in contravention of any of the provisions of this Act,
or any rule made there under,
(c) manufacture for sale or for distribution, any Ayurvedic, Siddha or Unani drug except
under, and in accordance with the conditions of, a licence issued for such purpose under
this Chapter by the prescribed authority : Provided that nothing in this section shall apply
to Vaidyas and Hakims who manufacture Ayurvedic, Siddha or Unani drug for the use of
their own patients : Provided further that nothing in this section shall apply to the
manufacture, subject to the prescribed conditions, of small quantities of any Ayurvedic,
Siddha or Unani drug for the purpose of examination,test or analysis.

Schedule Z (Proposed) : Requirements and guidelines for permission to manufacture of

ASU drugs for sale or to undertake clinical trials. The Ayurvedic Drug Manufacturers'
Association (ADMA) wants the Department of Ayush to take a gradual approach while
implementing the proposed draft notification on Schedule Z after considering requisite
change as suggested by the stakeholders. This demand was projected in the representation
that they recently sent to the government which elaborately highlighted the industry
issues and concerns over adopting the proposed draft notification. The association
stressed that industry is not against any progressive ideas offered by the government
provided that they are taken after considerable discussion and deliberation with the
stakeholders. The industry pointed out that they are open to consider the proposition,
however implied that the industry needs time to adjust to these changes. ADMA in their
representation suggested that the government should take a calculative approach focusing
on gradually implementing the so called changed in an organised and phased manner so
that the industry will not be forced to face the brunt of the changes. The association stated
that prior to coming out with regulatory changes the government should also take into
account the ability of the small scale industry in adopting to those proposed changes.
In brief these guidelines consists of information on the protocol, Ethical issues, Safety
considerations, informed consent process, data management, quality assurance, Record
keeping, Statistics and areas on special concern like studies with contraceptives, surgical
procedures , medical devices etc. Draft of this schedule is under consideration.