DRUG DEVELOPMENT

PROCESS

PH 107: PHARMACEUTICAL DOSAGE FORMS, DRUG

DELIVERY SYSTEM & MEDICAL DEVICES, LECTURE
02- New Drug Development & Approval Process
Learning Objectives:

 To define the different terms relating to drug discovery

process and development
 To understand the Drug Development Process
 To differentiate the various methods of drug discovery
 To explain the process of drug discovery and its other
components
TERMINOLOGIES
▪ Clinical Drug Materials (CTM)
- Dosage formulations used for clinical evaluation of a new
drug
▪ Investigational New Drug (IND)
- Protects the right & safety of the subjects
- ensures investigational plan is sound & designed to
achieve the stated objectives
▪ New Drug Application (NDA)
- Gains permission to market the drug product
▪ Supplemental New Drug Application (SNDA)
- Application by the sponsor of approved NDA to make
changes
 Abbreviated New Drug Application (ANDA)
- Nonclinical laboratory studies & clinical investigations
may be omitted, except those pertaining to the drug’s
bioavailability

 Biologics License Application (BLA)

- Manufacture of biologicals (blood products, vaccines, &
toxins)

 International Conference on Harmonization (ICH)

- Brings together regulatory requirements
- establishes (long range goal) a uniform set of standards
for drug registration within geographic areas
DRUGS SUBSTANCE
 active ingredient/component that produces
pharmacologic activity
 Produced by:
- chem. synthesis
- enzymatic reaction
- recovery from a natural product
- recombinant DNA tech. - fermentation
- combination of these processes
 Purification needed before use in a drug product
NEW CHEMICAL ENTITY (NCE)
 drug substance with unknown clinical, toxicologic, physical & chem.
properties

DRUG PRODUCT
 finished dosage form (containing the drug subs. + other
excipients/inert substances)
DRUGS
 Drugs refer to pharmaceutical products that pertain to
chemical compounds or biological substances, other
than food, intended for use in the treatment,
prevention, or diagnosis of disease in humans or
animals, including the following:
 (1) Any article recognized in the official United States
Pharmacopeia/National Formulary, Homeopathic Pharmacopeia of
the United States of America, Philippine Pharmacopeia, Philippine
National Drug Formulary, British Pharmacopoeia, European
Pharmacopoeia, Japanese Pharmacopoeia, and any official
compendium or any supplement to them

RA 10918
DRUGS
 (2) Any article intended for use in
diagnosis, cure, mitigation, treatment, or
prevention of disease of man or animals;
 (3) Any article, other than food, intended
to affect the structure or any function of
the human body or animals;
 Any article intended for use, as a
component of articles, specified in
clauses (1), (2) and (3), not including
devices or their components, parts and
accessories; and
 Herbal or traditional drugs as defined in
Republic Act No. 9502

RA 10918
SOURCES OF DRUGS
Plant sources

Animal sources

Mineral/ Earth sources

Microbiological sources

Synthetic/ Semi-synthetic sources

Genetic Engineering
A. PLANT SOURCES

 Plant materials have served as a

reservoir of potential drugs
 Conversion of botanic folklore
remedies into modern wonder drugs
 After isolation and structural
identification of active plant
constituents, it maybe recreated by
total synthesis
 Make use of the natural chemical as
the starting material and modified
them through molecular manipulation
Examples:

Rauwolfia Vinca rosea Vitex negundo Mangostana

serpentina garcinia
USES: USES:
USES: - Periwinkle - Lagundi Leaves USES:
are considered - Used to
- Chemical - Antidiabetic aromatic, bitter,
reserpine agent anti- treat skin
inflammatory, infections,
- Tranquilizer - Antitumor and bronchial wounds, dysent
- Hypotensive activity smooth muscle ery, and urinary
agent relaxant tract infections
 B. ANIMAL SOURCES
 Drug testing and biologic assay
 Provided drugs that are mannered from their tissues or through their biologic
processes
 EXAMPLES:
1. Pancreas is a source of Insulin, used in treatment of Diabetes.
2. Urine of pregnant women gives human chorionic gonadotropin (hCG) used for
the treatment of infertility.
3. Sheep thyroid is a source of thyroxin, used in hypertension.
4. Cod liver is used as a source of vitamin A and D.
5. Anterior pituitary is a source of pituitary gonadotropins, used in treatment of
infertility.
6. Blood of animals is used in preparation of vaccines.
7. Stomach tissue contains pepsin and trypsin, which are digestive juices used in
treatment of peptic diseases in the past.
Examples: Marine sources of drugs
C. MINERAL/ EARTH SOURCES

 Metallic and Non metallic sources:

1. Iron is used in treatment of iron deficiency anemia.
2. Mercurial salts are used in Syphilis.
3. Zinc is used as zinc supplement. Zinc oxide paste is
used in wounds and in eczema.
4. Iodine is antiseptic. Iodine supplements are also
used.
5. Gold salts are used in the treatment of rheumatoid
arthritis.
C. MINERAL/ EARTH SOURCES
 Miscellaneous Sources:
1. Fluorine has antiseptic properties.
2. Borax has antiseptic properties as well.
3. Selenium as selenium sulfide is used in anti dandruff
shampoos.
4. Petroleum is used in preparation of liquid paraffin.
D. MICROBIOLOGICAL SOURCES
 Include serums, antitoxins and vaccines
 In 1796, Edward Genner works on smallpox vaccine
 Poliomyelitis vaccine- renal monkey
 Mumps & Influenza vaccine- chick embryo
 Rubella (German measles) vaccine- duck embryo
 Other Examples:
1. Penicillium notatum is a fungus which gives penicillin.
2. Actinobacteria give Streptomycin.
3. Aminoglycosides such as gentamicin and tobramycin are
obtained from streptomycis and micromonosporas.
E. SYNTHETIC/ SEMI-SYNTHETIC
SOURCES
 i. Synthetic Sources:
 When the nucleus of the drug from natural source as well as its
chemical structure is altered, we call it synthetic.
 Examples include Emetine Bismuth Iodide
 ii. Semi Synthetic Source:
 When the nucleus of drug obtained from natural source is
retained but the chemical structure is altered, we call it semi-
synthetic.
 Examples include Apomorphine, Diacetyl morphine, Ethinyl
Estradiol, Homatropine, Ampicillin and Methyl testosterone.
 Most of the drugs used nowadays (such as antianxiety drugs,
anti convulsants) are synthetic forms.
F. GENETIC ENGINEERING
 Recombinant DNA & monoclonal antibody
 Recombinant DNA technology involves cleavage of DNA by
enzyme restriction endonucleases. The desired gene is
coupled to rapidly replicating DNA (viral, bacterial or
plasmid). The new genetic combination is inserted into the
bacterial cultures which allow production of vast amount of
genetic material.
 GENE THERAPY
 Is a medical intervention based on the modification of the
genetic material of living cells
 GOAL DRUG

 CHARACTERISTICS OF A GOAL DRUG:

 Specifically desired effect,
 Administered by the most desired route (generally orally)
at minimal dosage and dosing frequency
 Optimal onset and duration of activity
 Exhibit no side effects
 Eliminated in the body efficiently and completely
 Low cost
 Pharmaceutically elegant
 Physically & chemically stable
LEAD COMPOUND
 Are chemical compounds that show desired biological or
pharmacological activity and may initiate the
development of a new clinically relevant compound.
 Lead compounds are typically used as starting points in
drug design to give new drug entities.
 Drug design strategies can be used to improve the
compound’s pharmacodynamic and pharmacokinetic
properties.
 ORPHAN DRUG
 Treatment IND are sought for to target small number of
patients with rare conditions/diseases (orphan diseases)
where there are no satisfactory alternative treatments
ORPHAN DISEASE
- Rare disease/condition affecting fewer than 200,000
people:
*chronic lymphocytes *leukemia
*Gaucher’s disease *cystic fibrosis AIDS
PRODRUG
 The International Union of Pure and Applied Chemistry defines
a prodrug as a chemical that is transformed before it has
pharmacological effects.
 Before a prodrug can provide its intended effects in your body,
it needs to be broken down. A prodrug’s type affects how the
medication is transformed or activated — whether it occurs
inside or outside your cells.
 Different types of prodrugs can also impact drug interactions.
Certain interactions may prevent a prodrug from becoming
active.
 Prodrug vs Active drug

There are two major types of prodrugs. These categories are based
on how prodrugs are converted in the body:
1) Type I prodrugs turn into their active forms inside of cells.
2) Type II prodrugs turn into their active forms outside of cells, such
as in blood or other fluids.
NEW DRUG
 New Molecular Entity (NME)- is defined by FDA as an active
ingredient that has never before been marketed in any form.
 A change in a previously approved drug product’s formulation
or method of manufacture constitutes newness under the
law such as changes can alter the therapeutic efficacy
and/or safety of a product.
 A proposed new use for an established drug, a new dosage
schedule or regimen, a new route of administration, or a
new dosage form makes a drug or a drug product’s status
new and triggers reconsideration for safety and effficacy
DRUG NOMENCLATURE
 Empirical formula- indicates the number and relationship pf
the atoms in the molecule
 Example: Amoxicillin- C16H19N3O3S.3H2O
 Chemical name- name of the compound’s every part of
molecular structure
 Example: Amoxicillin- (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-
hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-
azabicyclo[3.2.0]heptane-2-carboxylic acid
DRUG NOMENCLATURE
 Generic name- non-propriety name of the drug, serves to
identify the substance to which is applies by means of a
designation that maybe used by the professionals, refers to
the active ingredient of the drug.
 Example: Amoxicillin
 Brand name- trademarked name/ marketed name assigned
by the producing company
 Example: Himox™, Amoxil™, Trimox™
BIOLOGICAL CHARACTERIZATION
 Prospective drug substances must undergo preclinical testing
for biologic activity to assess their potential as useful
therapeutic agents.
 Pharmacology
 Drug Metabolism
 Toxicology
 To evaluate whether a drug is safe and effective, information
must be gained on how it is absorbed, distributed throughout
the body, stored, metabolized, and excreted and how it
affects the action of the body’s cells, tissues, and organs.
1. PHARMACOLOGY
 The science concerned with drugs, their sources, appearance,
chemistry, actions and uses. It includes the biochemical and
physiologic effects, mechanism of action, absorption,
distribution, biotransformation, and excretion.
 Pharmacokinetics is the science that analyzes how the human
body interacts with a drug. Pharmacokinetics examines how
the drug is absorbed, distributed, metabolized, and excreted
by the body. Pharmacodynamics is the science that studies the
biochemical and physiologic effects of a drug and its organ-
specific mechanism of action, including effects on the cellular
level.
1. PHARMACOLOGY
 Another way to describe the difference between the 2 disciplines
is to say that pharmacokinetics is “what the body does to the
drug," whereas pharmacodynamics is “what the drug does to
the body.”
Pharmacologic Profile
 Among early studies are determination of compound’s selectivity
for various receptors and its activity against select enzyme
systems. Studies of the compound’s effects on cell function are
then performed to detect evidence of efficacy and to determine
whether the compound is an agonist or antagonist. Then followed
by studies with isolated animal tissues to define further the
compound’s activity and selectivity. Then whole animal studies are
used to evaluate the pharmacologic effects of the agent on
specific organ system.

Pre-clinical testing Clinical testing

Pharmacologic Profile
Animal studies
 The primary objective of the animal studies is to obtain
basic information on the drugs effects that maybe safe
and effective use in humans.
 Examples:
 Hypertensive studies- Dogs & rats
 Respiratory effects studies- Dogs & Guinea pigs
 Diuretic activities- Dogs
 Blood coagulation- Rabbits
 Central Nervous system studies- Mice and rats
2. DRUG METABOLISM
 Drug Metabolism involves those chemical process
within living organism to maintain life.
 Series of animal studies of a proposed drugs ADME are
undertaken to determine the following:
 Extent and rate of drug absorption from various route of
administration
 Rate of distribution of the drug through the body and the
site and duration of drug’s residence
 Rate, primary and secondary sites, mechanism of the
drug’s metabolism in the body
 Proportion of administered dose eliminated from the
body
2. DRUG METABOLISM
 Specific & non-specific enzymes
- Participate in drug metabolism (liver, kidneys, lung & git)
 Drugs following oral adm. that enter the hepatic
circulation after absorption from gut – exposed to rapid
drug metabolism
 1st pass effect – transit through the liver & exposure to the
hepatic enzyme system
 - to be avoided, other routes of adm (buccal, rectal)
may be used to absorb drug into the systemic circulation
through blood vessels other than hepatic
 ADME studies – performed through the collection &
analysis of urine, blood & feces samples, & careful exam.
Of animal tissues & organs upon autopsy
3. TOXICOLOGY
 Deals with the adverse or undesired effects of
drugs
 Preclinical safety evaluation or toxicity studies
 Determine:
 Substance’s potential for toxicity with short-term or long-
term use
 Substance’s potential for specific organ toxicity
 Mode, site and degree of toxicity
 Dose-response relationships over time
 Gender, Reproductive or teratogenic toxicities
 Substance’s carcinogenic and genotoxic potential
Different studies in toxicological
profile:

 A. Acute or short-term toxicity studies

- toxic effect of a test compound when administered in single
dose and/or multiple doses over short period, usually a single
day.
*test compd administered at various dose levels, with toxic
signs observed
*doses are ranged to find doses that do not to produce toxic
effect, severe toxic effect & intermediate toxic level
 B. Subacute or subchronic studies
- Considered:
- The relationship to projected human clinical studies
for safety

- Animal toxicity studies (minimum of two weeks of daily

drug administration at 3 or more dosage levels to two
animal species) are required to support the initial
administration of a single dose in human clinical testing
 C. Chronic toxicity studies

- drugs intended to be given to humans for a week or more,

animal studies of 90 to 180 days in length must
demonstrate safety
- For chronic human illness, long-term animal studies of 1
year or longer
 D. Carcinogenicity studies
 For limited no. of rat & mouse strains
- there is reasonable information on
spontaneous tumor incidence
 Long term studies (18-24 months) with surviving animals killed
& studied at defined weeks during the test period
 component of chronic testing, undertaken when the
compound has shown sufficient promise as a drug to enter
human clinical trials.
 E. Reproduction Studies
- reveals any effect of an active ingredient on mammalian
reproduction
- Evaluated for anatomical abnormalities, growth &
development: maternal parent, fetus, neonates & weaning
offspring
- Fertility & mating behavior, mutagenicity, teratology
 F. Genotoxicity or Mutagenicity Studies
- Determines whether test compd affects gene mutation or
cause chromosome or DNA damage
- Used in assays to detect mutations: Strains of Salmonella
typhimurium
Pre-Discovery Stage

PREFORMULATION

Finished Product
Raw Materials

Image Source: altexsoft.com

PREFORMULATION STUDIES

 Each drug substance has intrinsic chemical and

physical characteristics that must be considered
before the development of a pharmaceutical
formulation
 DRUG SOLUBILITY
 PARTITION COEFFICIENT
 DISSOLUTION RATE
 PHYSICAL FORM
 STABILITY
DRUG SOLUBILITY

 A drug substance administered by any route

must possess some aqueous solubility for
systemic absorption and therapeutic response
 Poorly soluble compounds may exhibit incomplete,
erratic, and/or slow absorption thus produce
minimal response at desired dosage
PARTITION COEFFICIENT
 A drug’s partition coefficient is a measure of
its distribution in a lipophilic- hydrophilic
phase system and indicates its ability to
penetrate biologic multiphase system
DISSOLUTION RATE
 It is the speed at which a drug substance dissolves
in a medium

 For a chemical entity, its acid, base, or salt

forms, as well as its physical form, may result in
substantial difference in dissolution rate
PHYSICAL FORM

 The crystal or amorphous forms and/ or the

particle size of a powdered drug can affect the
dissolution rate, thus the rate and extent of
absorption, for a number of drugs
 STABILITY
 Drug Stability testing at various temperature,
conditions of relative humidity (RH), durations, and
environments of light, air and packaging is
essential in assessing drug and drug product
stability
Investigational New drug
(IND)
 To protect the rights and safety of the subjects
and to ensure that the investigational plan is
sound and is designed to achieve the stated
objectives
The clinical protocol
 part of the IND application
 submitted to ensure the appropriate design and conduct
of investigation
 Includes:
*purpose & objectives *investigational plan
*number of patients *subject selection
*dosing plan *clin. procedures, lab. tests
*patient observations, measurements & tests, etc.
Pre-IND meetings
 FDA advises a sponsor relating to the preparation and
submission of IND on:
*scientific *technical *formatting concerns.
 Includes:
*advice on the adequacy of data to support an
investigational plan
* design of a clinical trial/ investigation produces
*data to meet requirements of the next step
*filing NDA to gain approval for marketing.
FDA Review of an IND Application
 The FDA’s objectives in reviewing IND:
• protect the safety and right of human subjects
• ensure evaluation of the drug’s safety & effectiveness.
• objections are best met by the accuracy and completeness
of the IND submission
• design & conduct of the:
*investigational plan *expertise *diligence of
the investigators.
FDA Drug Classification
System
 Upon receipt and examination of IND/NDA
application
 FDA classifies the drug by:
*chemical type * therapeutic potential.
PHASES OF PRODUCT DEVELOPMENT OF
DRUG PRODUCTS CONTG NCEs :
▪ Preclinical Stage
– Animal pharmacology & toxicology data are obtained
- determines the safety & efficacy of the drug
- submission of investigational new drug (IND) application
for human testing to the FDA

▪ Phase I
- initial introduction (Clinical testing)
- subjects: Healthy volunteers (20-100)
- determines drug tolerance & toxicity (assessing safety)
Phases of Clinical Investigation
 Phase II
- Controlled clinical studies to several hundred
patients with the disease/condition are treated
- Safety measured - determines the therapeutic
index (ratio of toxic dose to effective dose)
 final drug formulation developed bioequivalent
(same rate & extent of drug absorption to the brand
drug product) to the dosage form
Phases of Clinical Investigation
 Phase III
- several hundred to several thousand patients with
the disease/condition treated for which the drug
was developed (controlled and uncontrolled trials)
- Large scale, multicenter studies performed - to
determine safety & and efficacy
-Side effects are monitored
Phases of Clinical Investigation
 Phase 3a
- completed studies sufficient for the NDA
 Phase 3b
- Additional studies are used to gather:
*supplemental information to support certain labeling
requests
* information on patients’ quality of life issues
*product advantages over already marketed competing
drugs
*evidence in support of possible additional drug
indications
*other clues for prospective postmarketing studies
Phases of Clinical Investigation
 Submission of a new drug application (NDA)
- An NDA is submitted to the FDA for review &
approval when clinical trials are completed
 Phase IV
- Continual clinical investigation
- Manufacturing scale-up activities
- Drug formulation modified slightly
- To gather supplemental information (labeling,
product advantages, additional indications,
prospective postmarketing studies)
Phases of Clinical Investigation

 Phase V (POST MARKETING SURVEILLANCE)

 Product development continues after the FDA’s market
approval of drug product.
 Drug product may be improved due to equipment,
regulatory, supply or market demands
Phases of Clinical Testing:
 Phase No. of patients Length Purpose

Phase I 20-100 Several months Mainly safety

Phase II Up to several Several months to Some short term

hundred 2 years safety but mainly
effectiveness

Phase III Several hundred to 1- 4 years Safety,

several thousand Effectiveness,
dosage
STAGES OF DRUG DEVELOPMENT PROCESS
Post marketing reporting of adverse
drug experiences

 A drug sponsor is required to report to the FDA each

adverse drug experience that is both serious (life
threatening or fatal) and unexpected (not contained
in the approved drug product labeling) regardless of
the source of the information within 15 working days
of receipt information.
Factors in determining drug’s dose
 Age
 Body weight
 Sex
 Body surface are
 tolerance
 General health status
 Pathologic condition(s)
 Concomitant drug therapy
 Dosage form, time & route of administration
Drug Dosage and Terminology
 usual adult dose & starting dose for the patient -
amount of drug that produces the desired effect in
the majority of adult patient
 Dosage regimen/schedule of dosage determined
from:
* clinical investigation
* inherent duration of action
* pharmacokinetics
* characteristics of the dosage form.
 Units of activity
- Derived from biological assay methods
-reflects drug’s potency
- necessary when drug’s (antibiotics & endocrine
products) suitable chemical assay methods are
unavailable
 Minimum effective concentration (MEC)
- drug’s Average blood serum concentration
- Determines minimum concentration expected to
produce the drug’s desired effects in a patient
 Minimum toxic concentration (MTC)
- Second level of serum concentration of drug
- Above the average blood serum concentration level
producing toxic effects
- Negates desirable effects of the drug compromising
safety of the patient

 ED50/Median Effective Dose

- Produces the desired intensity of effect in 50% of
the individuals tested
 Median toxic dose
- Produces a defined toxic effect in 50% of the
individuals tested

 Therapeutic index
- Relationship between drug’s desired & undesired
effects
- Ratio of drug’s median toxic dose & median
effective dose, TD50/EF50
Drug Dosage and Terminology
 Maintenance dosage- regularly schedule
subsequent administration to keep the most
desirable concentration of drug in the blood
 Initial priming or loading dose required to attain
desired concentration of the drug in the blood of
tissues
 Prophylactic dose - protects the patient from
contracting the illness
 Therapeutic dose - administered to the patient
after exposure or contraction of the illness.
 Drug-drug interaction
- Effect of drug modified by prior/concurrent
administration of another drug
- Chemical or physical interaction between the
drugs/alteration of the absorption, distribution,
metabolism/excretion patterns of one of the drugs
- Include “social” agents (tobacco & alcohol) affecting
pharmacokinetics of a number of drugs & alter drug’s
usual dose
Treatment IND/treatment protocol

 use of an investigational drug in the life-

treating disease in lieu of no satisfactory
alternative therapy.
 makes promising new drug available to
desperately ill patient, early as possible in the
drug development process.
Withdrawal or Termination of
an IND
 By the sponsor any time ending all clinical
investigation
 stock of clinical supplies returned to the
sponsor/otherwise destroyed.
 If withdrawn because of safety reasons, must
advice: FDA, IRB, and all investigators
 FDA may terminate an IND for: safety, efficiency,
or regulatory compliance issue.
The New drug Application (NDA)

 Filed by the sponsor with the FDA if

- three phases of clinical testing demonstrates
sufficient drug safety and therapeutic effectiveness
 preceded by pre-NDA meeting between the sponsor
and FDA to discuss:
-consent and format of the new drug application.
* The purpose of NDA is to gain permission to market the
drug product
Drug product labeling

 According to federal regulation, includes:

*label placed on an immediate container
* information on the packaging, in package insert,
and in company literature, advertising, and
promotion materials
 The package insert required to contain the
summary information.
Drug Product Labeling
 Description
 Clinical Pharmacology
 Indications & usage
 Contraindications
 Warnings
 Precautions
 Adverse reactions
 Drug abuse & dependence
 Overdosage
 Dosage & administration
 How supplied
▪ completed New Drug Application:
- reviewed by the FDA, decides:
*to allow the sponsor to market the drug
*to disallow marketing
*to require additional data before
rendering a judgment
- FDA respond within 180 days (review
clock) of receipt of an application
FDA review and “Action Letters’

 Approvable Letter.
- specific additional data or other requested
material is submitted/specific conditions are met.
- pertains to development or wording of the final
product labeling.
 Approval Letter:
- Approval of the application permitting marketing
 Non Approvable Letter:
- one or more deficiencies.
International Conference on Harmonization
(ICH)

 Harmonizing/bringing together regulatory

requirements with long-range goal of
establishing a uniform set of standards for drug
registration within these geographic areas
 Focused on 3 general areas:
A. Quality B. safety C. efficacy
 Quality topics
- stability, light stability, analytical validation, impurities
& biotechnology
 Safety topics
- carcinogenicity, genotoxicity, toxicokinetics,
reproduction toxicity & single & repeat dose toxicity
 Efficacy topics
- population exposure, managing clinical trials, clinical
study reports, dose response, ethnic factors, good
clinical practices & geriatrics
Current Good Manufacturing
Practice (cGMP)
GMP
 Established by the Food and Drug Administration
(FDA) to ensure the minimum standards are met
for drug product quality
 Establish requirements for all aspects of
pharmaceutical manufacture
 FDA inspects the facilities and production records of
all the firms covered by these regulations
GMP for Finished Pharmaceuticals
 General provisions:  Packaging and labeling
Scope and Definition control
 Organization and  Holding and
Distribution
Personnel
 Laboratory controls
 Building and Facilities
 Records and Reports
 Equipment  Returned and Salvaged
 Control of drugs
Components,  Information technology
and Automation
Containers and
Closures
 Production and
Process control
Packaging, Labeling and Storage
of Pharmaceuticals
 The package and closure system must be shown effective for the
particular product for which it is intended:
 Physicochemical properties
 Light-transmission for glass or plastic
 Drug compatibility
 Leaching and/or migration
 Vapor transmission for plastic
 Moisture barrier
 Toxicity for plastics
 Valve, actuator, metered dose, particle size, spray
characteristics, and leaks for aerosols
 Sterility and permeation for parenteral
 Drug stability
 A container is “that which holds the article and is
or maybe in direct contact with the article.”

 Immediate container is “that which is in direct

contact with the article at all times.”
 A well-closed container- “protects the contents
from extraneous solids and from loss of the article
under ordinary conditions of handling, shipment,
storage, and distribution”

 A tight container- “protects the contents from the

contamination by extraneous liquids, solids, or
vapors, from loss of the article, and from
efflorescence, deliquescence, or evaporation under
the ordinary or customary conditions of handling,
shipment, storage, and distribution and is capable
of tight re-closure.”
 A hermetic container- “ is impervious to air or any other gas
under the ordinary or customary conditions of handling,
shipment, storage, and distribution.”
 A sterile hermetic containers are generally use to hold
preparations intended for injection or parenteral
administration.

 A single-dose container is one that holds a quantity of drug

intended as a single dose and when opened cannot be
resealed with assurance that sterility has been maintained.
 Includes: fusion-sealed ampuls, pre-filled syringes and
cartridges
 A multiple-dose container is a hermetic container
that permits withdrawal of successive portions of the
contents without changing the strength or
endangering the quality of purity of the remaining
portion.
 A single-unit container is designed to hold a
quantity of drug intended for administration as a
single dose promptly after the container is opened
 A single-unit package is termed a unit dose
package

 A multiple-unit container contain more than a

single unit or dose of the medication
Advantages of single-unit package:

 Positive identification of each dosage unit

 Reduction of medication errors
 Reduced contamination
 Protective wrapping
 Reduced dispensing time
 Greater ease of inventory control
 Less discarded medication
 Many pharmaceutical manufacturers require light-
resistant containers (good quality amber glass or light-
resistant opaque plastic)
 Reduce light transmission sufficiently to protect
light-sensitive pharmaceuticals
GLASS PACKAGING:

CONSTITUTION OF OFFICIAL GLASS TYPES

TYPE GENERAL DESCRIPTION
I Highly resistant borosilicate glass
II Treated soda lime glass
III Soda lime glass
NP General purpose soda lime glass
USE OF PLASTIC CONTAINERS:
 Lightness of weight and resistance to impact
 Reduction of transportation cost and losses
 Versatility in container design and consumer
acceptance
 Consumer preference for plastic squeeze bottles
 Ophthalmic, nasal sprays, lotions
 Popularity of blister packaging and unit-dose
dispensing
PLASTIC MATERIALS:

 Polyethylene terephthalate (PET)

 Amorphous polyethylene terephthalate glycol (APET)
 Polyethylene terephthalate glycol (PETG)

 APET & PETG- excellent transparency and luster and

can be sterilized with gamma radiation
USE OF PLASTIC CONTAINERS:
PROBLEMS ENCOUNTERED:
 Permeability of the containers to atmospheric
oxygen and to moisture vapor
 Leaching of the constituents of the container to
the internal contents
 Absorption of drugs from the contents to the
container
 Transmission of light through the container
 Alteration of the container upon storage
PERMEABILITY

 A process of solution and diffusion, with the

penetrant dissolving in the plastic on one side and
diffusing through to the other side
 Increase in temperature, pressure and use of additives
tend to increase the permeability of the plastic
 Glass containers are less permeable than plastic
containers
 Moisture vapor or gas can pose threat to the stability of
the product
PERMEABILITY

 Many capsule and other products are liable to

deteriorate in humidity unless protected by high-
barrier packaging
 Desiccant protectants, such as silica gel in small
packets, are commonly included as added protection
against the effect of moisture vapor
LEACHING

 A term used to describe the movement of components

of a container into the contents
 Polymer additives such as plasticizers, stabilizers or
antioxidants
 It maybe influenced by temperature, excessive
agitation of the filled container and solubilizing effect
of liquid content on one or more of the polymer
additives
SORPTION

 A term used to indicate the binding of molecules to

polymer materials, includes both adsorption and
absorption
 pH of a solution may affect the chemical nature of plastic
container
 excipients such as colorants, preservatives, or stabilizers
would likewise alter the quality of the product
 Deformations, softening, hardening and other physical
changes in plastic containers can be caused by the
action of the container’s contents or external factors,
including temperature and the physical stress placed
upon the container in handling and shipping
STORAGE
 To ensure the stability of a pharmaceutical preparation for
the period of its intended shelf life, the product must be
stored in proper condition.
Description Temperature range
COLD Not exceeding 8°C
Refrigerator: between 2°- 8°C
Freezer: between -25°C and-
10°C

COOL Between 8°C and 15°C

ROOM TEMPERATURE Between 20°C and 25°C
WARM Between 30°C and 40°C
EXCESSIVE HEAT Above 40°C
Protection from freezing: it subjects a product to loss of strength or
potency or to destructive alteration of the dosage form, it must bear
the label: protect the product from freezing
TRANSPORTATION

 Temperature and Humidity variations may occur

during shipment that is why special consideration
must be noted
END OF PRESENTATION ☺
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