Evaluation of Drugs WHO &ICH Guidelines for The Assessment of Herbal Drugs stability
Evaluation of Drugs WHO & ICH Guidelines for the
assessment of herbal drugs Stability
testing of herbal Drugs
K SUDHEER KUMAR
MAK COLLEGE OF PHARMACY , HYDERABAD
The International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use (ICH) is unique in bringing together the
regulatory authorities and pharmaceutical industry to discuss scientific and
technical aspects of pharmaceuticals and develop ICH guidelines. Since its
inception in 1990,
The ICH topics are divided into the four categories below and ICH topic codes are assigned
according to these categories.
Harmonisation achievements in the Quality area include pivotal milestones such as the
conduct of stability studies, defining relevant thresholds for impurities testing and a more
flexible approach to pharmaceutical quality based on Good Manufacturing Practice
(GMP) risk management.
ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like
carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a non-
clinical testing strategy for assessing the QT interval prolongation liability: the single most
important cause of drug withdrawals in recent years.
EFFICACY GUIDELINES The work carried out by ICH under the Efficacy heading is
concerned with the design, conduct, safety and reporting of clinical trials. It also covers
novel types of medicines derived from biotechnological processes and the use of
pharmacogenetics/genomics techniques to produce better targeted medicines.
MULTI DICIPLINARY Those are the cross-cutting topics which do not fit uniquely into one
of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology
(MedDRA), the Common Technical Document (CTD) and the development of Electronic
Standards for the Transfer of Regulatory Information (ESTRI).
ICH Introduction to ICH - The Quality Guidelines
Q 1 – Stability Testing
Q 2 – Analytical Validation
Q 3 – Impurities
Q 4 – Pharmacopoeias
Q 5 – Biotechnological Products
Q 6 – Specifications
Q 7 – Good Manufacturing Practices
Q 8 – Pharmaceutical Development
Q 9 – Quality Risk Management
Q 10 – Pharmaceutical Quality System
WHO GUIDELINES IN QUALITY
ASSESSMENT OF HERBAL DRUGS
For the purpose of these guidelines “Herbal medicine” should be regarded as : Finished,
labelled medicinal products that ,contain as active ingredient aerial or underground
parts of plants,or other plant material or combinations there of ,whether in the crude
state or as plant preparations.Plant material include juices,gums,fatty oils, essential oils
and any other substances of this nature.Herbal medicines may contain excipients in
addition to the active ingredients.Medicines containing plant material combined with
chemically defined,isolated constituents of plants, are not considered to be herbal
Exceptionally, in some countries herbal medicines may also contain, by tredition, natural
organic or inorganic active ingredients which are not of plant origin.
• The past decade has seen a significant increase in the use of herbal medicines .As a
result of WHO’s promotion of traditional medicines , countries have been seeking the
assisstance of WHO in
identifying safe and effective herbal medicines for use in national health care system.
• In both developed and developing countries, consumers and health care providers need
to be supplied with up-to-date and authoritative information on the beneficial properties
and possible harm full effects ,of all herbal medicines
To define basic criteria for the evaluation of quality,safety and efficacy of herbal
medicines and there by to assist national regulatory authorities,scientific
organisations and manufacturers to under take an assessment of the documentation
or submission in respect of such products.
As a general rule in this assessment, traditional experience means long term use as
well as the medical ,historical and ethonological background of those products shall
Assessment of Quality,Safety and Efficacy and Intended use:
This part should cover all important aspects of the quality assessment of herbal
medicines.However,if a pharmacopoeia monograph exists it should be sufficient to make
reference to this monograph. If no such monograph is avaliable, a momograph must be
supplied and should be set out in the same way as in an official pharmacopoeia.
All procedures should be in accordance with Good Manufacturing Practices [GMP].
Crude plant material:
The botanical definition,including genus,species and authority should be given to ensure
correct identification of a plant.A definition and description of the part of the plant from
which the medicine is made[eg;leaf, flower,root] has to be provided as well as an
indication as to whether fresh, dried or traditionally processed material is used.
The active and characteristics constituents should be specified and if,possible, content
limits should be defined.Foriegn matter,impurities and microbial content should be
defined or limited.vocher specimen, representing each lot of plant material
processed,should be authenticated by a qualified botanist and should be store for at least
a ten year period.
A lot number should be assigned and this should appear on the product lable.
Plant preparation should include powdered plant materials, extracts,tintures,fatty or
essential oils,expressed juices and preparations whose production involves a
fractionation, purification or concentration process.The manufacturing process should
be described in detail.If any other
substance is added during the manufacture,to adjust the plant preparation to a
certain level of active or characteristic constituents or for any other purpose,the added
substsnce should be mentioned in the procedure description.
A method for identification, and where possible assay of plant preparation should be
added.If the identification of an active principle is not possible,it should be sufficient to
identify a characteristic substance or mixture of substances(eg;chromatographic
fingerprint)to ensure consistent quality of preparation
• The manufacturing procedure and formula including the amount of excipients should be
described in detail.
• A method of identification,and where possible quantification,of the plant material in
product should be defined.
• If the identification of an active principle is not possible,it should be sufficient to
identify a characteristic substsance or mixture of substance(eg,chromatographic
fingerprinting)to ensure consistent quality of the product.
• For important finished produts,confirmation of regulatory status in the country of the
origin should be required;the WHO certification scheme on the quality of the
pharmaceutical products moving in International Commerce should be applied.
The physicsal and chemical stability of the product in the final marketing container should
be tested under defined storage conditions and the shelf-life should be established.
This part should cover all the relavent aspects of the safety assessment of a medicinal
product has been traditionally used with out demonstrated harm no specific restrictive
regulatory action should be undertaken unless new evidence demands a revised risk-
If any toxicological studies are available, they should be part of the assessment.If a
toxicological risk is known, toxicity data have to be submited.Risk assessment, whether it
is independent of dose (eg,special danger allergies) ,or whether it is a function of dose
should be documented.
Assessment of Efficacy and Intended use:
This part should cover all the important aspects of efficasy assessment .A review of the
relavent literature should be carried out and copies provided of the original articles or
proper references to them.
The pharmocological and clinical effects of the active ingredients and,if known,their
constituents with therapeutic activity shoud be specified or described.
Evidence required to support indications:
The indications for the use of medicine should be specified.In the case of traditional
medicines,the requrements for proof of efficacy shall depend on the kind of indication
• As many herbal remedies consist of a combination of several active ingredients, and as
experience on the use of traditional remedies is often based on he combination of
products,the assessment should differentiation between old and new combinations
products. Identical requrements for the assessment of old and new combinations would
result in an appropriate assessment of certain traditional medicines.
• In the case of traditionally used combination products,the documentation of traditional
use and experience may serve for documentation of efficacy.
• In ordeer to justify the efficacy of a new ingredient and its positive effect on the total
combination,clinical studies may be reqired.
Product Information for the Consumer:
The labelling of the products and the package insert should be understandable to the
consumer/patient. The package informstion should cover all necessary information on
the proper use of product.
The following elements of information usually suffice:
Name of the product
Quantitave list of active ingredient
- dosage(if appropriate,specified for children and the elderly)
- mode of administration
- duration of use
- major adverse effects,if any
- over dosage information
- contraindication,warnings,precautions and major drug indications
- use during pregnancy and lactation
- expiry date
- lot number
-holder of the marketing authorisation
-Identification of the active ingredient by the latin botanical name,in addition to the
-common name in the language of preference of national regulatory authority is
Advertisements and other promotional activities to health personnel and the lay public
should be fully consistent with the approved package information.
Utilization of guidelines:
WHO guidelines for the assessment of herbal medicines are intended to facilitate the
work to e carried out by regulatory authority, scientific bodies and industry in the
development , and assessment and registration of such products.
The effective regulation and control of herbal medicines moving in international
require close liaison with appropriate national institutions that are able to keep under
regular review all aspects of their production and use , as well as to conduct or sponser
evaluative studies of their efficacy,toxicity,safety,acceptability, cost and relative value
compared with other drugs used in modern medicine.
Safety is a fundamental principle in the provision of herbal medicines and herbal
products for health care, and a critical component of quality control. These guidelines
provide practical technical guidance for monitoring the safety of herbal medicines
within pharmacovigilance systems. The safety monitoring of herbal medicines is
compared and contrasted with that of other medicines currently undertaken in the
context of the WHO International Drug Monitoring Programme.
For the safety of those using herbal medicines, four complementary actions are
needed: ♦ clear identification of the nature of adverse events ♦ management of the
risks ♦ institution of measure to prevent adverse events ♦ good communication of the
risks and benefits of herbal medicines.
Objectives The objectives of these guidelines are to:
♦ support Member States, in the context of the WHO International Drug Monitoring
Programme, to strengthen national pharmacovigilance capacity in order to carry out
effective safety monitoring of herbal medicines
♦ provide technical guidance on the principles of good pharmacovigilance and the
inclusion of herbal medicines in existing national drug safety monitoring systems; and
where these systems are not in place, to facilitate the establishment of an inclusive
national drug safety monitoring system
♦ provide standard definitions of terms relating to pharmacovigilance, and safety
monitoring of herbal medicines
♦ promote and strengthen internationally coordinated information exchange on
pharmacovigilance, and safety monitoring of herbal medicines among Member States
♦ promote the safe and proper use of herbal medicines. The regulation of herbal
medicines and their place in national health-care systems differs from country to country,
and these guidelines will therefore need to be adapted to meet the needs of the local
Quality control of phytomedicine
The quality control of phytopharmaceuticals may be defined as the status of a drug,
which is determined either by identity, purity, content, and other chemical, physical or
biological properties, or by the manufacturing process.
Quality control is based on three important pharmacopeial definitions:
• Identity: Is the herb the one it should be?
• Purity: Are there contaminants, e.g., in the form of other herbs which should not be
• Content or assay: Is the content of active constituents within the defined limits?
Parameters for Quality Control of Herbal Drugs
1 Microscopic Evaluation
Quality control of herbal drugs has traditionally been based on appearance and today
microscopic evaluation is indispensable in the initial identification of herbs, as well as in
identifying small fragments of crude or powdered herbs, and detection of foreign matter
and adulterants. A primary visual evaluation, which seldom needs more than a simple
magnifying lens, can be used to ensure that the plant is of the required species, and that
the right part of the plant is being used. At other times, microscopic analysis is needed to
determine the correct species and/or that the correct part of the species is present. For
instance, pollen morphology may be used in the case of flowers to identify the species,
and the presence of certain microscopic structures such as leaf stomata can be used to
identify the plant part used. Although this may seem obvious, it is of prime importance,
especially when different parts of the same plant are to be used for different treatments.
Stingin nettle (Urtica urens) is a classic example where the aerial parts are used to treat
rheumatism, while the roots are applied for benign prostate hyperplasia.
2.Determination of Foreign Matter
Herbal drugs should be made from the stated part of the plant and be devoid of other
parts of the same plant or other plants. They should be entirely free from moulds or
insects, including excreta and visible contaminant such as sand and stones, poisonous
and harmful foreign matter and chemical residues. Animal matter such as insects and
“invisible” microbial contaminants, which can produce toxins, are also among the
potential contaminants of herbal medicines . Macroscopic examination can easily be
employed to determine the presence of foreign matter, although microscopy is
indispensable in certain special cases (for example, starch deliberately added to
“dilute” the plant material). Furthermore, when foreign matter consists, for example,
of a chemical residue, TLC is often needed to detect the contaminants
3 Determination of Ash
To determine ash content the plant material is burnt and the residual ash is measured as
total and acid-insoluble ash. Total ash is the measure of the total amount of material
left after burning and includes ash derived from the part of the plant itself and acid-
insoluble ash. The latter is the residue obtained after boiling the total ash with dilute
hydrochloric acid, and burning the remaining insoluble matter. The second procedure
measures the amount of silica present, especially in the form of sand and siliceous earth
4 Determination of Heavy Metals
Contamination by toxic metals can either be accidental or intentional. Contamination by
heavy metals such as mercury, lead, copper, cadmium, and arsenic in herbal remedies
can be attributed to many causes, including environmental pollution,and can pose
clinically relevant dangers for the health of the user and should there-fore be limited .
The potential intake of the toxic metal can be estimated on the basis of the level of its
presence in the product and the recommended or estimated dosage of the product. This
potential exposure can then be put into a toxi-cological perspective by comparison with
the so-called Provisional Tolerable Week-ly Intake values (PTWI) for toxic metals, which
have been established by the Foodand Agriculture Organization of the World Health
A simple, straightforward determination of heavy metals can be found in many
pharmacopoeias and is based on color reactions with special reagents such as
thioacetamide or diethyldithiocarbamate, and the amount present is estimated by
comparison with a standard. Instrumental analyses have to be employed when the
metals are present in trace quantities, in admixture, or when the analyses have to be
quantitative. The main methods commonly used are atomic absorption
spectrophotometry (AAS), inductively coupled plasma (ICP) and neutron activation
analysis (NAA) .
5 Determination of Microbial Contaminants and Aflatoxins
Medicinal plants may be associated with a broad variety of microbial contaminants,
represented by bacteria, fungi, and viruses. Inevitably, this microbiological background
depends on several environmental factors and exerts an important impact on the overall
quality of herbal products and preparations. Risk assessment of the microbial load of
medicinal plants has therefore become an important subject in the establishment of
modern Hazard Analysis and Critical Control Point (HACCP) schemes.
Herbal drugs normally carry a number of bacteria and molds, often originating in the soil.
Poor methods of harvesting, cleaning, drying, handling, and storage may also cause
additional contamination, as may be the case with Escherichia coli or Salmonella spp.
While a large range of bacteria and fungi are from naturally occurring microflora, aerobic
spore-forming bacteria frequently predominate.
Laboratory procedures investigating microbial contaminations are laid down in the
well-known pharmacopoeias, as well as in the WHO guidelines . Limit
values can also be found in the sources mentioned.
In general, a complete procedure consists of determining the total aerobic microbial
count, the total fungal count, and the total Enterobacteriaceae count, together with
tests for the presence of Escherichia coli, Staphylococcus aureus, Shigella, and
Pseudomonas aeruginosa and Salmonella spp.
The European Pharmacopoeia also specifies that E. coli and Salmonella spp. should be
absent from herbal preparations . However it is not always these two pathogenic
bacteria that cause clinical problems. For example, a fatal case of listeriosis was
caused by contamination of alfalfa tablets with the Grampositive bacillus Listeria
Materials of vegetable origin tend to show much higher levels of microbial
contamination than synthetic products and the requirements for microbial
contamination in the European Pharmacopoeia allow higher levels of microbial
contamination in herbal remedies than in synthetic pharmaceuticals.
The allowed contamination level may also depend on the method of processing of the
drug. For example, higher contamination levels are permitted if the final herbal
preparation involves boiling with water .
The presence of fungi should be carefully investigated and/or monitored, since some
common species produce toxins, especially aflotoxins. Aflatoxins in herbal drugs can
be dangerous to health even if they are absorbed in minute amounts .
Aflatoxin-producing fungi sometimes build up during storage . Procedures for the
determination of aflatoxin contamination in herbal drugs are published by the WHO .
After a thorough clean-up procedure, TLC is used for confirmation.
In addition to the risk of bacterial and viral contamination, herbal remedies may also
be contaminated with microbial toxins, and as such, bacterial endotoxins and
mycotoxins, at times may also be an issue . There is evidence that medicinal plants
from some countries may be contaminated with toxigenic fungi (Aspergillus, Fusarium).
Certain plant constituents are susceptible to chemical transformation by contaminating
microorganisms.Withering leads to enhanced enzymic activity, transforming some the
constituents to other metabolites not initially found in the herb. These newly formed
constituent(s) along with the molds such as Penicillium nigricans and P. jensi may then
have adverse effects.
6 Determination of Pesticide Residues
Even though there are no serious reports of toxicity due to the presence of pesticides and
fumigants, it is important that herbs and herbal products are free of these chemicals or at least are
controlled for the absence of unsafe levels.
Herbal drugs are liable to contain pesticide residues, which accumulate from agricultural practices,
such as spraying, treatment of soils during cultivation, and administering of fumigants during
storage. However, it may be desirable to test herbal drugs for broad groups in general, rather than
for individual pesticides. Many pesticides contain chlorine in the molecule, which, for example, can
be measured by analysis of total organic chlorine. In an analogous way, insecticides containing
phosphate can be detected by measuring total organic phosphorus.
Samples of herbal material are extracted by a standard procedure, impurities are removed by
partition and/or adsorption, and individual pesticides are measured by GC, MS, or GC/MS. Some
simple procedures have been published by the WHO and the European Pharamacopoeia has laid
down general limits for pesticide residues in medicine.
7 Determination of Radioactive Contamination
There are many sources of ionization radiation, including radionuclides, occurring in the
environment. Hence a certain degree of exposure is inevitable. Dangerous
contamination, however, may be the consequence of a nuclear accident. The WHO, in
close cooperation with several other international organizations, has developed
guidelines in the event of a widespread contamination by radionuclides resulting from
major nuclear accidents. These publications emphasize that the health risk, in general,
due to radioactive contamination from naturally occurring radio nuclides is not a real
concern, but those arising from major nuclear accidents such as the nuclear accident in
Chernobyl, may be serious and depend on the specific radionuclide, the level of
contamination, and the quantity of the contaminant consumed. Taking into account the
quantity of herbal medicine normally consumed by an individual, they are unlikely to be
a health risk. Therefore, at present, no limits are proposed for radioactive
STANDARDIZATION AND QUALITY CONTROL PARAMETERS FOR EVALUATION OF
HERBAL CRUDE DRUGS
According to WHO (1996a and b, 1992), standardization and quality control of herbal
crude drugs is the process involving the physicochemical evaluation of crude drugs
covering the aspects as, selection and handling of crude drug materials, safety, and
efficacy and stability assessment of finished products, documentation of safety and risk
based on experience provision of product information to consumer and product
Macroscopic Examination: In case of whole drugs, the macroscopic and secondary
characters are sufficient for identification of right variety and search of adulterants.
Microscopic Examination: These are valuable both for powders and ungrounded drugs for
identification of right variety and search of adulterants.
Solubility: The solubility, especially exceptional behavior toward solvent, is useful in
examination of many oils and olio – resins.
Physical Constituents: Physical constituents such as specific gravity, optical rotation,
viscosity and refractive index are especially valuable for the evaluation of facts, oleo –
resins, balsams and similar substances.
Foreign Organic Matter: Remove off matter other than source plant to get the drug in
Swelling Index: It measures the swelling property of the medical plant.
Ash Values: It is criteria to judge the identity and purity of crude drug – total ash, sulfated
ash, water soluble ash and acid insoluble ash etc.
Extractive Values: These are indicating the approximate measure of chemical constituents
of crude drug.
Moisture Content: To check moisture content helps prevent degradation of product.
Crude Fiber: To determine excessive woody material. Criteria for judging purity.
Chromatographic examination: Include identification of crude drug based on use of major
chemical constituent as marker.
Qualitative Chemical Evaluation: Covers criteria for identification and characterization of
crude drug with respect to phytochemical contents.
Quantitative Chemical Evaluation: Covers criteria to estimate the amount of active
Volatile Oils: It covers the measurement of the volatile content of the plant.
Bitterness Value: The bitter properties of plant material are determined by comparing the
threshold bitter concentration of an extract of the materials with that of a dilute soluble of
guanine hydrochloride R.
Hemolytic Activity: The hemolytic activity of plant materials, or a preparation containing
saponins, is determined by comparison with that of a reference material, saponin R.
Foaming Index: The foaming ability of an aqueous decoction of plant materials and their
extracts is measured in terms of a foaming index.
Pesticide Residues: It measures the pesticide residues in the plant.
Arsenic and heavy metals: Contamination of medicinal plant materials with arsenic and heavy
metals can be attributed to many causes including environmental pollution and traces of
Microorganisms: Current practices of harvesting, handling and production may cause addition
contamination and microbial growth.
Aflatoxins: Minute presence in crude drug can be toxic and hence their presence is being tested.
DNA Fingerprinting: Technique is useful for identification of phytochemically indistinguishable
genuine drug from substituted or adulterated drug.
Chemical Fingerprinting: To allow the detection of all the components in extracts.
Biological Profiling: It identifies the biological active plants allowing highly sophisticated
standardization and quality control.
Radioactive Contamination: A certain amount of exposure to ionizing radiation cannot be avoided
since they are many sources, including radio nuclides occurring naturally in the ground and the
Toxicological Studies: To help determine pesticide residue, potentially toxic elements, safety
studies in animals like LD50 and microbial count approach to ascertain their presence or absence.
W.H.O GUIDELINES FOR QUALITY STANDARDIZED HERBAL FORMULATIONS
Standardization and quality control parameter for herbal formulations are
based on the following fundamental parameters:
Quality control of crude drugs material, plant preparations and finished
Stability assessment and shelf life.
Safety assessment; documentation of safety based on experience or
Assessment of efficacy by ethnomedical information and biological activity
Regulatory authorities worldwide have issued regulations or guidelines for stability
testing parameters and testing procedures for herbal products stored in proposed
conditions. These testing parameters and methods for finished herbal products are
detailed in the guidelines and regulations issued by 5 global authorities and 15 countries,
that is, the Association of Southeast Asian Nations (ASEAN), the Eurasian Economic
Commission (EEC), the European Medicines Agency (EMA), the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH),
the World Health Organization (WHO),
The maintenance of herbal product quality during storage is critical for guaranteeing
therapeutic activity. Stability testing is used to evaluate how herbal products retain their
properties under specified storage conditions stressed by heat, moisture, light, oxygen,
various physical and chemical conditions (e.g., vibration or freezing), and container-related
Herbal products are produced in various dosage forms (e.g., tablets, powders, or liquids
for oral administration or as creams for external application), and thus, stability testing of
various dosage forms requires appropriate methods.
The stabilities of finished herbal products can be determined by testing for properties
susceptible to storage conditions and include physical (organoleptic characteristics,
physical condition, particle size, etc.), chemical (assays of active components, pH,
identification, etc.), microbial, and toxicological properties. These properties can all affect
the qualities, safeties, or the efficacies of herbal products, and thus, the shelf lives of
herbal products should be determined by stability testing
According to the EMA guidelines, all herbal medicinal products should be tested for the
compliance with specifications including descriptions, identifications, assay, impurities,
and microbial limits. The following testing parameters are also specified: tablets (coated
and uncoated) and hard capsules (dissolution, disintegration, hardness, friability,
uniformity of mass, water content, and microbial limits); oral suspension (uniformity of
mass, pH, microbial limits, antimicrobial preservative content, antioxidant preservative
content, extractables, alcohol content, dissolution (for oral suspensions), and
resuspension (for dry powder products), particle-size distribution, redispersibility,
rheological properties for relatively viscous solutions or suspensions, viscosity, specific
gravity (for oral suspensions, relatively viscous, or nonaqueous solutions), reconstitution
time, and water content); and herbal teas (loss on drying, identification, purity,
uniformity of mass or average mass of the sachet, assay, particle size, and microbial
quality or microbial limit testing)
ICH guidelines provide general requirements for the storage stability testing of new drug products
that cover chemical substances with respect to description, identification, assay, and impurity
contents However, we consider ICH guidelines are also applicable to herbal products as global
documents regulated by EMA, Australia, Japan, or Switzerland are conducted in accordance with
ICH guidelines. The parameters for stability testing of specific dosage forms are as follows: tablets
(coated and uncoated) and hard capsules (dissolution, disintegration, hardness, friability,
uniformity of dosage units, water content, and microbial limits); oral liquids (uniformity of dosage
units, pH, microbial limits, antimicrobial and antioxidant preservative content, extractables,
alcohol content, dissolution, particle-size distribution in oral suspensions, redispersibility for oral
suspensions, rheological properties for relatively viscous solutions or suspensions, reconstitution
time, and water content); parenteral drug products (uniformity of dosage units, pH, sterility,
endotoxins, pyrogens, particulate matter, water content, antimicrobial and antioxidant
preservative content, extractables, functionality testing of delivery systems including prefilled
syringes, autoinjector cartridges, or the equivalent, osmolarity, particle-size distribution for
injectable suspensions, redispersibility, and reconstitution time)
The WHO expert committee publishes technical reports annually on specifications for
pharmaceutical preparations and guidelines on good herbal processing practices for
General requirements of the stabilities of finished pharmaceutical products include
appearance, assay, and degradation products and preservative and antioxidant content.
Specific parameters are also provided according to dosage forms of the product, that is, as
liquids, solids, or others .
Liquid herbal dosage forms include fluid extracts, decoctions, infusions, tinctures, syrups,
and oral solutions, which are tested for precipitate formation, clarity, pH, viscosity,
extractables, and microbial contamination level. Oral suspensions are tested for
precipitate formation, clarity, pH, viscosity, extractables, microbial contamination level,
dispersibility, rheological properties, mean size or distribution of particles, and
polymorphic conversion. Oral emulsions are tested for precipitate formation, clarity, pH,
viscosity, extractables, microbial contamination level, phase separation, and globule
mean size or distribution. For aromatic water, and powders or granules for oral solutions
or suspensions, water content and reconstitution time are tested
Solid herbal dosage forms include herbal tea bags, plant powders, dry extract powders,
granules, pills, hard gelatin capsules, soft gelatin capsules, tablets, and lozenges. Hard
gelatin capsules are tested for brittleness, dissolution, disintegration, water content,
and microbial contamination level. Soft gelatin capsules are tested for dissolution,
disintegration, microbial contamination level, pH, leakage, and pellicle formation.
Tablets are tested for dissolution, disintegration, water content, hardness, and friability
Other dosage forms include ointments, creams, and salves which are tested for clarity,
homogeneity, pH, suspendability (for lotions), consistency, viscosity, particle-size
distribution (for suspensions), microbial contamination level, sterility, and weight loss.
Ophthalmic and otic products (e.g., creams, ointments, solutions, and suspensions) are
tested for sterility, particulate matter, and extractable volume. Inhalers are tested for
dose content uniformity, labelled number of medication actuations per container that
meet stated dose delivery, aerodynamic particle-size distribution, microscopic
evaluation, water content, leak rate, level of microbial contamination, valve delivery or
shot weight, extractables or leachables from plastic and elastomeric components,
weight loss, pump delivery, foreign particulate matter, extractables or leachables from
plastic, and elastomeric components of the container, closure, and pump. Plasters and
patches are tested for in vitro release rates, leakage, level of microbial contamination,
sterility, peel strength, and adhesive forces. Medicated oils are also included in other
dosage forms, but testing parameters are not provided