Stability Testing of Herbal Preparations

STABILITY is officially defined as the time

lapse(period) during which drug substance retains
the same properties and characteristics
At the time of Manufacturing
•Physical, Chemical, Microbiological, Therapeutic
and Toxicological specifications are evaluated
• To maintain its identity, strength, quality, and purity
 Stability Testing of Herbal Medicinal Products


India has seen tremendous growth in development of herbal
drug formulations.

Majority of them comprising of polyherbal formulations.

Many of these, constituents present in the drug may react
with each other raising the serious concern about the stability
of such formulations.

Therefore evaluation of the parameters based upon chemical,
physical, microbiological, therapeutic and toxicological
studies can serve as an important tool in stability studies.
 Purpose Stability Testing of Herbal Products

Stability testing is necessary to ensure that the product is of



satisfactory quality throughout its entire storage period.


Stability studies should be performed on at least three production
batches of the herbal products

To provide proof on how the quality of the herbal products varies
under the influence of environmental factors temperature, light,
oxygen, moisture, excipients in the dosage form, particle size of drug,
microbial contamination, trace metal contamination.

To establish a recommended storage condition and shelf-life.
Factors Affecting Stability Testing
of Herbal Preparations

Stability testing of herbal drugs is a challenging risk,
because the entire herb or herbal product is regarded as
the active matter.

In some cases only constituents with defined
therapeutic activity are known

Stability data can also be generated under
accelerated atmospheric conditions of
temperature, humidity and light, which is referred
to as short term stability and the data so obtained
is used for predicting shelf-life of the product.
 Factors Affecting Stability Testing of Herbal
Preparations


Stability testing should be conducted on the dosage
form packaged in the container closure system
proposed for marketing.

With the help of modern analytical techniques like
spectrophotometry, HPLC, HPTLC to generate a
sound stability data of herbal products and predict
their shelf-life.
Stability Testing of Poly Herbal Medicinal Products

Ayurvedic and Chinese herbal medicines, there

may be 10 or even 20 individual herbal
ingredients.

 The proposed quality standards will be difficult,

if not impossible in many cases, to apply to these
complex herbals.

 The only way that these data might be provided

for combinations of several herbs is by the use of
HPLC & HPTLC
 Specific Characteristics of Herbal Medicinal
Products


From the chemical and analytical point of view,
herbal drugs, herbal preparations are complex in
nature.

This is due to the high number of constituents
belonging to different chemical classes and having
different analytical behaviours.

For example, flavanoids versus essential oils.

In many cases, these constituents have only very low
concentrations in the finished product.
 Types of Extracts

standardized extract:- Herbal extract that has been

processed so that it contains a specified amount of a
certain compound, usually the one thought to be the
active compound. Example, silymarines in Silybum
marianum.
 Guarantee the constant quality of the end product,

 Higher concentration of active ingredients 

 Kept for longer periods 

 Higher level of bio-availability:

 More easily absorbed by the body

Quantified extracts are limited to a defined range of
constituents that are known to contribute to
therapeutic activity – for example, hypericines in
Hypericum perforatum.

Quantification: means adjusting the herbal

preparation to a defined range of constituents
exclusively achieved by blending different batches of
herbal substances

 Other extracts without known effective constituents

are essentially defined by their production process
and their specifications.
 Choice of Markers


To calculate the quantity of a herbal substance,
single chemically-defined constituents or groups
of constituents by known standard which is called
as ‘markers’.
These are also called ‘active markers’ for
quantified extracts and ‘analytical markers’ for
other extracts.
 Monographs

Monographs may be a helpful tool to define a marker and can

give helpful information about a suitable method.

The monograph methods used only which mentioned in the

pharmacopoeia.

 These methods are not applicable for a finished product

containing this drug substance because the resulting
concentration is too low, or matrix effects lead to a lack of
selectivity.
 Choice of Methods

Due to the complex composition of herbal preparations,
an analysis for quality is done by running high
performance liquid chromatography (HPLC) or gas
chromatography (GC) and thin layer chromatography
(TLC) methods, quantitative determinations by UV-
visible spectroscopy and HPTLC.


HPLC, HPTLC and GC methods have the benefit that a
specific fingerprint chromatogram for identification and
purity testing, as well as the detection of single
compounds for assay, is possible during one analysis.
 Ongoing Stability


According to GMP Guidelines for ongoing stability
testing, All formulations have to be tested.

All finished products and bulk products also have to be
tested.

Tests have to be carried out continuously – usually one
batch a year.

Studies are to be carried out continuously over the period
of the labelled shelf-life.
 Shelf-Life Specifications


Consider and identify issues related to the organoleptic,
physical, chemical, biological and microbiological
characteristics of the components under long term storage.

Consider the impact that manufacturing, packaging,
labeling, and holding/warehouse processes.

Consider the suitability of accelerated stability studies on
new herbal products. Components may react differently at
increased temperatures or humidity levels than normal
conditions.

Consider the potential for the formation of degradation
products.

Also written records related to the product must be retained
for one year past the shelf-life date.
 Selection of Batches


Stability data should be gathered on batches that are
representative of the product and container-closure system
being marketed.

After an expiration date is established or confirmed
initially, it may be appropriate to place a new batch of
production shelf-life study under long-term conditions
annually or more frequently.
Stability and Safety Parameters
 Types of Testing
Tablets
• Appearance, color, odor, taste; and mouthfeel
• Chemical fingerprints (TLC, HPLC, HPTLC, GC)
• Assay [i.e., label claim ingredient(s)]
• Hardness/friability
• Disintegration or dissolution rate
• Moisture content
• Microbial content (e.g. Total Bacterial Count, Total
Yeast & Mold count)
• Fat oxidation
• Ingredient degradation products
• Loss on drying
 2. Capsules (hard and soft)

Appearance, color, odor, taste; and/or mouthfeel

• Chemical fingerprints (TLC, HPLC, HPTLC, GC)
• Assay [i.e., label claim ingredient(s)]
• Disintegration or dissolution rate
• Capsule integrity such as brittleness or leakage
• Moisture content
• Microbial content (e.g. Total Bacterial Count, Total
Yeast & Mold count)
• Fat oxidation
• Ingredient degradation products
• Loss on drying
 3. Liquids and semi-solids (gels)

Appearance, color, odor, taste, and/or mouthfeel

• Chemical fingerprints (TLC, HPLC, HPTLC, GC)
• Assay [i.e., label claim ingredient(s)]
• pH
• Viscosity and/or texture
• Moisture content and/or water activity
• Microbial content (e.g. Total Bacterial Count, Total
Yeast & Mold count)
• Preservative content
• Fat oxidation
• Ingredient degradation products
• Loss on drying
 4. Powders
Appearance, color, odor, taste, and/or mouthfeel
• Chemical fingerprints (TLC, HPLC, HPTLC, GC)
• Assay [i.e., label claim ingredient
• Moisture content and/or water activity
• Microbial content (e.g. Total Bacterial Count, Total
Yeast & Mold count)
• Fat oxidation
• Ingredient degradation products
• Hygroscopicity
• Loss on drying