Quality Assurance of Herbal Formulations

Quality Assurance of Herbal Formulations
INTRODUCTION
Herbal drugs have been used since ancient times as medicines for the treatment of a range of
diseases. Medicinal plants have played a key role in world health. In spite of the great advances
observed in modern medicine in recent decades, plants still make an important contribution to
health care. Over the past decade, interest in drugs derived from higher plants, especially the
phytotherapeutic ones, has increased expressively.1 Herbs have created in interest among the
people by its clinically proven effects like immunomodulation, adaptogenic and antimutagenic
etc.2 it is estimated that about 25% of all modern medicines are directly or indirectly derived
from higher plant.
According to the World Health Organization (WHO), because of poverty and lack of access to
modern medicine, about 65-80% of the world's population which lives in developing countries
depends essentially on plants for primary health care.1 Also the overuse of synthetic drugs which
results in higher incidence of adverse drug reactions, have motivated the humans to go back to
nature for safer remedies.2 India is the 8th largest country having a total of around 47,000 plant
species, out of which more than 7,500 species have medicinal values. Among these medicinal
plants only 800 species are claimed to be in use and around 120 species are used in large
quantities.3 Currently the major pharmaceutical companies have demonstrated renewed interest
in investigating higher plants as a source for new lead structures and also for the development of
standardized phytotherapeutic agents with proved efficacy, safety and quality. 1 It is now
increasingly accepted worldwide that screening natural products is a more effective strategy for
discovering new chemical entities as natural product libraries have a broader distribution of
molecular properties such as molecular mass, octanol-water coefficient and diversity of ring
systems when compared to synthetic and combinatorial counter parts.3
The expanded use of herbal medicines worldwide has led to concerns relating to its safety,
quality and effectiveness. The quality control of herbal crude drugs and there formulations is of
paramount importance in justifying their acceptability in modern system of medicine. One of the
major problem faced by user industry is non- availability of rigid quality control profiles and
evaluationparametersforherbalformulations.4
1
HISTORY
Herbal medicine is the oldest form of healthcare known to mankind. Herbs had been used by all
cultures throughout history. It was an integral part of the development of modern civilization.
The plants provided food, clothing, shelter, and medicine. Much of the medicinal use of plants
seems to have been developed through observations of wild animals, and by trial and error. They
methodically collected information on herbs and developed well-defined herbal pharmacopoeias.
Indeed, well into the 20th century much of the pharmacopoeia of scientific medicine was derived
from the herbal lore of native peoples. Many drugs commonly used today are of herbal origin.
Indeed, about 25% of the prescription drugs dispensed in the United States contain at least one
active ingredient derived from plant material. Some are made from plant extracts; others are
synthesized to mimic a natural plant compound.
The use of plants as medicine is older than recorded history. As mute witness to this fact
marshmallow root, hyacinth, and yarrow have been found carefully tucked around the bones of a
Stone Age man in Iraq. These three medicinal herbs continue to be used today. Marshmallow
root is a demulcent herb, soothing to inflamed or irritated mucous membranes, such as a sore
throat or irritated digestive tract. Hyacinth is a diuretic that encourages tissues to give up excess
water.
The first U.S. Pharmacopoeia was published in 1820. This volume included an authoritative
listing of herbal drugs, with descriptions of their properties, uses, dosages, and tests of purity. It
was periodically revised and became the legal standard for medical compounds in 1906. But as
Western medicine evolved from an art to a science in the nineteenth century, information that
had at one time been widely available became the domain of comparatively few. Once scientific
methods were developed to extract and synthesize the active ingredients in plants,
pharmaceutical laboratories took over from providers of medicinal herbs as the producers of
drugs. The use of herbs, which for most of history had been mainstream medical practice, began
to be considered unscientific, or at least unconventional, and to fall into relative obscurity.
2
Early humans recognized their dependence on nature in both health and illness. Led by instinct,
taste, and experience, primitive men and women treated illness by using plants, animal parts, and
minerals that were not part of their usual diet. Physical evidence of use of herbal remedies goes
back some 60,000 years to a burial site of a Neanderthal man uncovered in 1960 .4 In a cave in
northern Iraq, scientists found what appeared to be ordinary human bones. An analysis of the soil
around the bones revealed extraordinary quantities of plant pollen that could not have been
introduced accidentally at the burial site. Someone in the small cave community had consciously
gathered eight species of plants to surround the dead man. Seven of these are medicinal plants
still used throughout the herbal world.4 All cultures have long folk medicine histories that
include the use of plants. Even in ancient cultures, people methodically and scientifically
collected information on herbs and developed well-defined herbal pharmacopoeias. Indeed, well
into the 20th century much of the pharmacopoeia of scientific medicine was derived from the
herbal lore of native peoples. Many drugs, including strychnine, aspirin, vincristine, taxol,
curare, and ergot, are of herbal origin. About one-quarter of the prescription drugs dispensed by
community pharmacies in the United States contain at least one active ingredient derived from
plant material. 5
Middle East medicine. The invention of writing was a focus around which herbal knowledge
could accumulate and grow. The first written records detailing the use of herbs in the treatment
of illness are the Mesopotamian clay tablet writings and the Egyptian papyrus. About 2000 B.C.,
King Assurbanipal of Sumeria ordered the compilation of the first known materia medica--an
ancient form of today's United States Pharmacopoeia--containing 250 herbal drugs (including
garlic, still a favorite of herbal doctors). The Ebers Papyrus, the most important of the preserved
Egyptian manuscripts, was written around 1500 B.C. and includes much earlier information. It
contains 876 prescriptions made up of more than 500 different substances, including many
herbs.5Greece and Rome. One of the earliest materia medica was the Rhizotomikon, written by
Diocles of Caryotos, a pupil of Aristotle. Unfortunately, the book is now lost. Other Greek and
Roman compilations followed, but none was as important or influential as that written by
Dioscorides in the 1st century A.D., better known by its Latin name De Materia Medica. This
text contains 950 curative substances, of which 600 are plant products and the rest are of animal
3
or mineral origin.5 Each entry includes a drawing, a description of the plant, an account of its
medicinal qualities and method of preparation, and warnings about undesirable effects.
Muslim world. The Arabs preserved and built on the body of knowledge of the Greco-Roman
period as they learned of new remedies from remote places. They even introduced to the West
the Chinese technique of chemically preparing minerals. The principal storehouse of the Muslim
materia medica is the text of Jami of Ibn Baiar (died 1248 A.D.), which lists more than 2,000
substances, including many plant products. Eventually this entire body of knowledge was
reintroduced to Europe by Christian doctors traveling with the Crusaders. Indeed, during the
middle Ages, trade in herbs became a vast international commerce.
East India. India, located between China and the West, underwent a similar process in the
development of its medicine. The healing that took place before India's Ayurvedic medical
corpus was similar to that of ancient Egypt or China (i.e., sickness was viewed as a punishment
from the gods for a particular sin). Ayurvedic medicine emerged during the rise of the
philosophies of the Upanishads, Buddhism, and other schools of thought in India. Herbs played
an important role in Ayurvedic medicine. The principal Ayurvedic book on internal medicine,
the Characka Samhita, describes 582 herbs.8
By the Later Han Dynasty (25-220 A.D.), medicine had changed dramatically in China. People
grew more confident of their ability to observe and understand the natural world and believed
that health and disease were subject to the principles of natural order. However, herbs still played
an important part in successive systems of medicine. The Classic of the Materia Medica,
compiled no earlier than the 1st century A.D. by unknown authors, was the first Chinese book to
focus on the description of individual herbs. It includes 252 botanical substances, 45 mineral
substances, and 67 animal-derived substances. For each herb there is a description of its
medicinal effect, usually in terms of symptoms. Reference is made to the proper method of
preparation, and toxicities are noted.8
Since the writing of the Classic of the Materia Medica almost 2,000 years ago, the traditional
Chinese materia medica has been steadily increasing in number. This increase has resulted from
the integration into the official tradition of substances from China's folk medicine as well as from
4
other parts of the world. Many substances now used in traditional Chinese medicine originate in
places such as Southeast Asia, India, the Middle East, and the Americas. The most recent
compilation of Chinese materia medica was published in 1977. The Encyclopedia of Traditional
Chinese Medicine Substances (Zhong Yao da ci dian), the culmination of a 25-year research
project conducted by the Jiangsu College of New Medicine, contains 5,767 entries.
5
Here is a brief history of key dates in the development of herbal medicines: (8)
2800BC First written record of herbal medicines, the Pen Ts'ao by Shen Nung
c400BC First Greek herbal written; Hippocrates develops principles of diet, exercise and
happiness as the cornerstones of health
c100BC First illustrated herbal produced in Greece
c50AD Roman Empire spreads herbal medicine and commerce of plants around the
Empire
c200AD Herbal practitioner, Galen, creates system for classifying illnesses and remedies
c500AD Hippocrates' principles followed in Britain by Myddfai practitioners throughout

Saxon times
c800AD Monks now pioneer herbal medicine with infirmaries and physic gardens at every
monastery
1100sAD Arab world now major influence on medicine and healing practices.
Physician Avicenna writes the Canon of Medicine
6
1200sAD Black Death spreads across Europe; 'qualified' apothecaries try bleeding, purging,
mercury and arsenic to stem the epidemic with no more success than traditional
herbalists
1500sAD Henry VII promotes herbal medicine in the face of the growing number of
untrained apothecaries and other 'medical practitioners' flourishing in London
Various Acts of Parliament passed to introduce some regulation of medical

practices including protection for 'simple herbalists' to practice without fear of
prosecution
1600sAD Society sees the first two-tier health system emerge - herbs for the poor and
exotics (plant, animal or mineral extracts) or 'drugs' for the rich
Nicholas Culpepper writes his famous herbal: The English Physician, explaining in
simple terms the practice of herbal medicine
1700sAD Preacher Charles Wesley advocates a sensible diet, good hygiene and herbal
medicine as the keys to a healthy life
1800sAD Herbal medicines begin to be eclipsed by mineral-drug based treatments. With

powerful drugs such as calomel (mercury) and laudanum available over the
counter serious side effects begin to be documented.
Albert Coffin pioneers low-cost herbal remedies using plants from his native
America as well as European ones helping hundreds of working class people at
his north of England practice.
Burgeoning pharmaceuticals industry makes herbal medicine seem outdated.

National Association of Medical Herbalists founded to defend the practice. Later to
become the National Institute of Medical Herbalists
1900sAD Medicinal herbals used extensively during World War I as drugs are in short
7
supply.
Post war period sees enormous expansion in the international pharmaceuticals

industry and the discovery of penicillin
A handful of dedicated herbalists keep the tradition alive.
A Modern Herbal by Hilda Level is published.
Pharmacy & Medicines Act 1941 withdraws herbal practitioner’s rights to supply
patients with medicines. Public outcry ensures the Act is never enforced.
After much campaigning by the NIMH, the Medicines Act in 1968 reinstates
practitioners' rights and the British Herbal Medicine Association is founded.
The BHMA produce the British Herbal Pharmacopoeia.
Revised edition is published in 1990. Public concern starts to grow over the side
effects of the 'wonder drugs' of the 1950s and their impact on the environment.
2000AD EU legislation advocates all herbal medicines should be subject to compulsory

clinical testing comparable to that undertaken for conventional drugs. Thus all
herbal medicines would be licensed.
UK government currently considering the possible impact and public perception of

this legislation.
Chapter - 2
8
QUALITY
ASSURANCE
9
Quality Assurance
Quality of a product is a very hot topic nowadays, and especially in the pharmaceutical
industry.Indeed, the regulatory authorities have paid special attention to quality in this
particular industry, due to the high risk of damage of life and health of patients possible, and
developed many guidelines to insure a sufficient level of quality. Quality is not any more
considered achieve able by strict adherence to, and verification of, specifications of
measurable parameters but has to be generated by a systematically planned and guided
process. Quality is not any more the sole responsibility of a central quality department but
requires the engaged participation of the entire work force.12
It is defined as the fulfillment all the requirements, legal and experience based, connected
with all aspects of manufacturing of high quality herbal medicinal products. It starts from the
beginning, the specification, processing and procurement of herbal starting material, follows
the procedure and quality considerations surrounding the intermediates and ends with
devising and monitoring the final production steps towards the final medicinal product.12
Quality assurance is therefore defined as a network. It encompasses the control and
documentation mechanism, which insure, that the multitude of regulations pertaining to and
used in practice of the pharmaceutical industry.
Assurance of product quality depends on more than just proper sampling and adequate
testing of various components and the finished dosage form. Prime responsibility of
maintaining product quality during production rests with the manufacturing department.
Removal of responsibility from manufacturing for producing a quality product can result in
imperfect composition, such as ingredients missing , sub potent or super potent addition of
ingredients , or mix up of ingredients ; mistakes in packaging or filling , such as product
contamination , mislabeling , or deficient package ; and lack of conformance to product
registration .Quality assurance personnel must establish control or checkpoints to monitor the
quality of the product as it is processed and upon completion of the manufacture .These begin
with raw materials and the component testing and include in-process , packaging ,labeling ,
and finished product testing as well as batch auditing and stability monitoring.13
10
In context with pharmaceutical industry quality assurance can be represented as:

Quality assurance = GAP + GHP + GMP + GLP + other measures
GAP = Good agriculture practices.
GHP = Good harvesting practices.
GMP = Good manufacturing practices.
GLP = Good laboratory practices.
Good agriculture practices:
The guidelines for GAP of medicinal herbs is intended to apply to the growing and primary
processing of such plants traded and used in therapy . Hence, it applies to the production of
all plants materials used in the food, feed, medicinal, flavoring and perfume industries.
The main aim in this GAP is to ensure that the plant raw material meets the demand of the
consumer and the standards of the highest quality.11
Good harvesting practices:
The starting materials for all phyto medicines are plant drugs. Mostly parts or plant organs of
medicinally used species and usually in the dried form. According to WHO, there are 21,000
plant species as being medicinally used as plant drugs. Between 70%-90% of these are
commercially obtained by collecting the drugs in the natural habit. Among these only about
50 – 100 species are cultured by PTC technique.11
11
Good manufacturing practices:
To deliver to the public life saving drugs of the highest quality and purity , the
pharmaceutical industry traditional has cooperate with FDA, even in recent years, when the
regulatory agencies have become increasingly restrictive.
This is a wide ranging concept concerning all matter that individually or collectively
influence the quality of product. It is the totally of the arrangement made with the object of
ensuring that product are of the quality required for their intended use.
The system quality assurance appropriate to the manufacturer of the pharmaceutical product
shall ensure that:
(a) The pharmaceutical are designed and developed in a way that takes account of the
requirements of GMP and other associated codes such as those of GLP and GCP.
(b) Adequate arrangements are made for manufacturer, supply and use of correct starting
and packaging materials.
(c) Adequate control on starting materials, intermediate products and bulk products and
other in process controls, calibration and validation are carried out.
(d) The finished product is correctly processed and checked in accordance with
established procedure.
(e) The pharmaceutical products are not released for sale product supplied before
authorized persons have certified that each production batch have been produced and
controlled in accordance with the requirements of the label claim and any other
provisions relevant to production, controlled and release of the pharmaceutical
products.11,20
12
Good laboratory practices:

It is a quality system for testing laboratory. Implementation of GLP will result in reliable
data. Although US FDA GLP are applicable to non clinical laboratory studies that support or
are intended to support application for research or marketing permits for
Products regulated by the Food and Drug administration, but many elements of these GLP
are of universal application. These are two important functions every testing laboratory will
involve in via:-
• Inspection and test
• Sampling 12
Quality assurance of herbal drugs:-

Quality assurance of herbal products may be assured by proper control of the herbal
ingredients and by means of GMP.Some herbal products have many herbal ingredients with
only small amount of individual herbs being present. Chemical and chromatographic
tests are useful for developing finished products specifications. Stability and shelf life of
herbal products should be established by the manufacture .There should be no difference in
standard set for the quality of different dosage forms; such as tablet and capsule of herbal
remedies as well as from those of other pharmaceutical preparation.
In UK, for the licensed herbal remedies the European scientific cooperative for phytotherapy
(Escop) monographs are an important development. In India the majority of the herbal
remedies available are being marketed for a long time, in fact, for many products it may be
before D and C act 1948.The condition, in other developing countries for the sale and
production of herbal products are similar to UK.
Quality, safety and efficacy of herbal drugs have to ensure to provide sound scientific footing
to enhance consumer confidence and to improve business prospects for herbal medicines.11
13
Quality assurance and quality control confusion
 Quality Assurance: A set of activities designed to ensure that the development

and/or maintenance process is adequate to ensure a system will meet its
objectives.
 Quality Control: A set of activities designed to evaluate a developed work
product.
QA activities ensure that the process is defined and appropriate. Methodology and standards
development are examples of QA activities. A QA review would focus on the process
elements of a project - e.g., are requirements being defined at the proper level of detail.
QC activities focus on finding defects in specific deliverables - e.g., are the defined
requirements the right requirements
Testing is one example of a QC activity, but there are others such as inspectionsThe
difference is that QA is process oriented and QC is product oriented. Testing therefore is
product oriented and thus is in the QC domain. Testing for quality isn't assuring quality, it's
controlling it.
Quality Assurance makes sure you are doing the right things, the right way.Quality Control
makes sure the results of what you've done are what you expected.
 The term “quality assurance” and “quality control” is sometimes used
interchangeably, but there is an important difference. Quality control generally refers
to testing of raw material, packaging components, and final product for conformance
to established requirements .quality assurance is a term that includes quality control,
but has broader meaning to include procedures, personnel training, record keeping
and facility design and monitoring. The philosophy of a quality assurance program is
to build quality into the product, rather than to rely only on final product testingto cull
out defective product.16
14
Chapter – 3
GENERAL CONCEPT
15
GENERAL CONCEPT
The following concepts are important in the development and setting of specifications. They
are not universally applicable, but each should be considered in particular circumstances.
1) Characterization:-
Consistent quality for products of herbal origin can only be assured if the starting plant
materials are defined in a rigorous and detailed manner. Characterization of a herbal
substance/preparation or herbal medicinal product is therefore essential to allow
specifications to be established, which are both comprehensive and relevant.
a) Macroscopic/microscopic characterization:
Macroscopic characterizations of medicinal plant material are based on the shape, size,
color, surface characteristics, texture, fracture and appearance.
• Color :-
The color is of use in indicating the general origin of the drug, e.g. material derived
from the aerial part of the plant is usually green and the underground plant materials
is usually devoid of green color.
• Size :-
The length, width and thickness of the crude materials is of great importance while
evaluating a crude drug. A graduate ruler in millimeter is adequate for this
measurement.
• Odor and Taste :-
Odor and taste of a crude material are extremely sensitive criteria based on
individual’s perceptions. The strength of the odor like weak, distinct, strong is first
determined and then odor sensation like musty, moldy, rancid, fruity, aromatic etc.are
determined.
16
• Surface characteristic – Texture and Fracture:-
The texture is best examined by taking a small quantity of material and rubbing it
between the thumb and forefinger, it is usually described as ‘smooth’, ‘rough’ ,
‘gritty’ . Touch of the material determines its softness or hardness. Bend and rupture
caused to the sample provides information of the brittleness and appearance of the
fractured plane as fibrous, smooth, rough, granular, etc.All this characteristic are
valuable in indicating the general type of material and the presence of more than one
component.11
Microscopic characterization is mainly depends on the parts of the plants such as
leaves, stems, flowers, fruits, seeds, barks, woods, underground drugs , entire
organisms, unorganized drugs.15
 Leaf Constants
 Palisade Ratio: It is defined as average number of palisade cells

beneath each epidermal cell. It can be determined with powdered
drugs.
 Vein – islet number: It is defined as the number of vein –islets per

sq.mm of the leaf surface midway between the midrib and the margin.
Levin in 1929 determined vein- islet number of several dicot leaves.
 Vein- termination number: It is defined as the number of vein let

termination per sq.mm of the leaf surface midway between the midrib
and the margin.
 Stomatal number: It is average number of stomata per sq.mm of

epidermis of the leaf.5
17
 Stomatal index: It is the percentage which the number of stomata

forms to the total number of epidermal cells; each stoma being counted
as one cell. It is calculated by using the following equation:-
S.I. = S / E + S x 100
Where, S.I. = Stomatal index
S = Number of stomata per unit area
E = Number of epidermal cells in the same unit area 15
 Trichomes:
These are another important diagnostic characters helpful in the identification of

drugs and detection of adulterants.Trichomes(fig1) are the tubular elongated or
glandular outgrowth of the epidermal cell.Trichomes is also called plant hairs.
Depending upon the structure and the number of cells present in trichomes, they
are classified as:15
 Covering trichomes or non-globular trichomes or Clothing trichomes
 Glandular trichomes
 Hydathodes or special type of trichomes.15
Fig.1 Trichomes
18
 Stomata:
The primary and most important function of stomata(fig2)is gaseous exchange

and the secondary function is transpiration. However, it is generally observed
that stomata are abundantly present in dicot leaves. Dicotyledons stomata are
classified into following types depending upon the form and arrangement of
subsidiary cells.15
 Paracytic or rubiaceos or parallel- celled stomata
 Diacytic or caryophyllaceous or cross-celled stomata
 Anisocytic or cruciferous or unequal-celled stomata
 Anomocytic or ranunculaceous or irregular-celled stomata
Fig.2 Stomata
19
 Quantitative Microscopy:
 Lycopodium spore method
It is an important analytical technique for powered drugs, especially when

chemical and other methods of evaluation of crude drugs fail as accurate measure
of quality. It is inexpensive technique with official status. Lycopodium spores are
very characteristics in shape and appearance and exceptionally uniform in size
(25µm). On an average, 94,000 spores per mg of powdered lycopodium are
present.15
N x W x 94,000x 100 / S x M x P = % Purity of Drug
Where,
N = number of characteristic structures (e.g. starch grains)in 26 fields
W =weight in mg of lycopodium taken
S = no. of lycopodium spores in the same 25 fields
M =weight in mg of the sample, calculated on basis of sample dried at 105 °C
P =2, 86,000 incase of ginger starch grains powder
20
b) Phytochemical characterization:
Analytical data on constituents including constituents with known therapeutic activity as well
as compounds suitable as active markers or analytical markers include chromatographic
fingerprinting.
A chromatographic finger print profile represents qualitative/ quantitative determination of

various components present in a complex plant extract irrespective whether or not their exact
identity is known. In view of the enormous progress made during the four decades,
standardization of botanical raw material in respect of active ingredient or marker substance
poses no problem. The advances made in the separation science have given clear advantage
to the chromatographic methods over the conventional trimetric and spetrophotometric
methods. Thin layer chromatographic technique, the simplest least expensive, provides of
wealth of information on the composition of medicinal plant drugs and its preparations, thus
it is the technique of choice for the positive identification of the raw material. In view of the
TLC’s limitations in quantitative analysis, liquid chromatography, which provides
simultaneous separation and detection, is the technique of choice for quantitative
determination of active ingredients or marker substances. The HPTLC technique combines
selectivity and sensitivity thus providing stability indicating features.
Non-chromatographic Assays (Gravimetric, Titrimetric, and Spectrophotometric) Simpler

techniques that give a broader idea of different classes of compounds present in the herb or
the polyherbal product being tested. Example: Total Tannins, Total glycosides, etc. Hence
some of these assays are non-specific in their results yet valuable quantitative tools in the
absence of marker compounds.
Chromatographic Techniques (TLC, HPTLC, HPLC, GC): More specific, accurate and
versatile techniques for analysing phytoconstituents present in single herbs or mixtures
thereof. Usually require "marker compounds" or "reference standards" which can be
procured from specialized companies or generated by us.
21
Depending on the availability of test methods, marker compounds and budget of the client, a
suitable technique or mix of methods can be employed to develop a standard testing method
for the study sample. This analytical protocol is then transferred to the client so that
subsequent tests can be performed at any other competent and equipped lab of their choice.11
c) Impurities:
Impurities can be classified as follows:
-impurities arising from starting materials (active substances, excipients) and containers
-process related impurities arising from the manufacturing process.
• Contaminants, which are impurities such as heavy metals, pesticides, mycotoxins,

fumigants as well as microbial contamination, including those arising extraneous
sources, and radioactive substances, if relevant.
• Degradation products, due to the particular nature of herbal medicinal product,

should primarily address toxicologically relevant impurities arising from
degradation of herbal substances/preparations.
• Residual solvents, which are impurities arising from manufacturing processes.
22
2) Design and development considerations:
The experience and data accumulated during the development of a herbal

substance/preparation or herbal medicinal product should form the basis for the setting of
specifications. In general, it is only necessary to test the herbal medicinal product for quality
attributes uniquely associated with the particular dosage form and the herbal substance or
herbal preparation present. For e.g. it may be possible to propose excluding or replacing
certain test on this basis some example is:
-reduced testing for pesticides residues where a herbal substance is grown under strict
organic cultivation without pesticides etc and potential contamination from adjacent
plantations has been eliminated,
-excluding or reducing tests for microbial limit in herbal preparations such as extracts or
tinctures depending on the ethanol content if justified by scientific evidence.
3) Pharmacopoeial tests and acceptance criteria:
The Indian Herbal pharmacopoeia contains important requirements pertaining to certain

analytical procedures and acceptance criteria that are relevant to herbal substances, herbal
preparation and their herbal medicinal products. Whenever they are appropriate,
pharmacopoeial methods should be utilized.
Drying and Storage of Plant Drugs

Drying
Drying consists of removal of sufficient moisture content of the crude drug so as to improve
its quality and make it resistant to growth of microorganisms. The process adopted for drying
is one of the parameters which affect the final quality of the drug. If enzyme action is to be
encouraged, slow drying at a moderate temperature is necessary. If enzymatic action is not
desired, drying should take place as soon as possible after collection. Drugs containing
volatile oils are liable to lose their aroma if not dried or if the oil is not distilled from them
immediately and all moist drugs are liable to develop mould. For these reasons, drying
apparatus and stills should be3 situated as near to the growing plants as possible. This has the
23
further advantage that freightage is much reduced, as many fresh drugs contain a
considerable amount of water.
The duration of the drying process varies from a few hours to many weeks and in the case of
open- air drying depends largely on the weather.
Drying by artificial heat is more rapid than open-air drying and is often necessary in places
where humidity is high. Artificial heating may be done by continuous belt driers or by means
of open fires stoves or hot-water pipes. In all drying sheds there must be a space of at least 15
cm between superimposed trays and air must circulate freely17,18,19.
Storage:-
Preservation of the plant drugs needs sound knowledge of their physical and chemical
properties. Quality of drugs can be maintained, if these are preserved properly. All the drugs
should be preserved in well closed and, preferably in the completely filled containers. The
premises which are water-proof, fire-proof and preferably rodent-proof are ideal for storage.
Radiation due to direct sun-light also causes destruction of active chemical constituents,e.g.
ergot, cod liver oil and digitalis. Squill, when stored in powdered form becomes very much
hygroscopic and forms rubbery mass on prolonged exposure to air. Atmospheric oxygen is
also destructive to several drugs and hence these are filled completely in well closed
containers, or the air in the container is replaced by inert gas like nitrogen; e.g. shark liver
oil, papain, etc.17,18,19
24
PESTICIDE RESIDUES AND MICROBIAL COUNT

Pesticide residue
The use of pesticide in the agricultural sector has greatly reduced the presence of insects,
fungi, and moulds in the plants. However, prolonged or excessive usage of pesticides on the
crop ultimately toxicants the entire plant material causing several health hazards. Limits for
pesticide residue should be established based on the recommendations of the Food and
Agriculture Organization (FAO) and the World Health Organization (WHO). These
recommended guidelines for food and animal feed provide the analytical methodology of
pesticide residues.17,18
Classification of pesticide
A classification based on the chemical composition and structure of the pesticide can be
made as follows:
• Chlorinated hydrocarbons and related pesticides: Aldrin, benzene hexachloride(BHC)
or hexachlorocyclohesane(HCH) , chlordane, dieldrin, endrin, heptachlor
• Chlorinated phenoxyalkanoic acid herbicides: 2,4-D; 2,4,5-T
• Organophosphorus pesticides: Carbophenothion , chlorthion coumaphos, demeton,
dichlorvos, dimethoate, ethion, fenchlorphos.
• Carbamate insecticides: Carbaryl
• Dithiocarbamate fungicides: Ferbam, maneb, nabam, thiram.
• Inorganic pesticides: Aluminium phosphide, calcium arsenate, lead arsenate
• Pesticides of plant origin: Tobacco leaf and nicotine; pyrethrumflower, extract
• Miscellaneous: Bromopropylate. Chloropicrin, ethylene dibromide.
Methods for the determination of pesticide residues
Chromatography and other procedures are the most successful when determining pesticide
residues. Samples are extracted by a standard procedure, impurities are removed by partition
and adsorption and the presence of a moderately-broad spectrum of pesticides is measured in
a single determination. However, these techniques are not universally applicable. As a result
of limitations in the analytical technique and incomplete knowledge of pesticide interaction
25
with the environment, it is not yet possible to apply an integrated set of methods which will
satisfy all situations.17,18
Maximum limit of residues for medicinal plant materials:
The maximum residue limit(MRL) for medicinal plant materials, including their preparations
such as tinctures, extracts, oils etc. should be defined within the limits of pesticide residue set
by the FAO/WHO Codex. Since the medicinal plant materials are usually taken in much
smaller quantities than other food products, the MRL can be calculated based on the
maximum acceptable daily intake (ADI) of pesticides for humans and the maximum daily
dose (MDD) of the medicinal plant material.
Where the nature of the pesticide to which the plant material has been exposed is unknown ,
it is necessary to determine only the content of total chlorine and to base the calculation on
the MRL of the most toxic chlorine- containing pesticide.18,19
4) Periodic/Skip testing:
Periodic or skip testing is the performance of specified tests at release on pre-selected batches
and/or at predetermined intervals, rather than on batch to batch basis. This represents a less
than full schedule of testing and should therefore be justified and presented to the regulatory
authority prior to implementation .This concept may be applicable to , for example
,dissolution ,residual solvents, and microbiological testing,e.g.,for solid dosage forms. This
concept may therefore sometimes be implemented post approval in accordance with GMP
and approval by the regulatory authority.
5) Release versus shelf life acceptance criteria: The concept of different

acceptance criteria for release versus shelf life specifications applies to herbal medicinal
products. This concept can also apply in exceptional cases to herbal substances and herbal
preparations, if justified. It pertains to the establishment of more restrictive criteria for the
release of a herbal medicinal product than are applied to the shelf life .Example where they
are applicable include assay or impurity (degradation product) levels.
26
6) In process tests:
In-process tests are tests, which may be performed during the manufacturing of either the
herbal preparation or herbal medicinal product, rather than as part of the formal battery of
tests which are conducted prior to product release. In-process tests, which are used for the
purpose of adjusting process parameters within an operating range, e.g., hardness and
friability of tablet cores, which will be coated, are not included in the specification. Certain
tests conducted during the manufacturing process, where the acceptance criteria are identical
to or tighter than the release requirement, (e.g. of a solution) may be used to satisfy
specification requirements when the tests is included in the specification.
7) Reference standard:
A reference standard, or reference material, is a substance prepared for use as the standard in
an assay, identification, or purity test. In the case of herbal medicinal products, the reference
standard may be a botanical sample of the herbal substance, a sample preparation e.g. extract
or tincture or a chemically defined substance e.g. a constituents with known therapeutic, an
active marker or an analytical marker or a known impurity. The composition of reference
standards of herbal substance and herbal preparations intended for use in assays should be
adequately controlled and the purity of a standard should be measured by validated
quantitative procedures.
27
• Herbal samples
If the herbal substance is not described in the European pharmacopoeia or in another

pharmacopoeia of a member state , a herbarium sample of the whole plant or part of
the plant, if the whole plant is a tree etc.,must be available.
To prepare a pooled sample for herbal drugs is very difficult as most of the foreign matters
are adhered to the medicinal plant material, which are intrinsically non-uniform. That is why
it is crucial that the size of the sample should be sufficiently large to be considered as a true
representative. In the case of whole drug, a weighed quantity (50-500gm) according to the
type of the drug is taken as sample.11
28
Chapter 4
HERBAL SUBSTANCES
AND
HERBAL PREPARATIONS
Herbal Substances
These are all mainly whole, fragmented or cut plants, plant parts, algae, fungi, lichen, in an
unprocessed, usually dried form but sometimes fresh. Certain exudates that have not been
subjected to a specific treatment are also considered to a herbal substance. Herbal substances
are precisely defined by the plant part used and the botanical name according to the binomial
system (genus, species, variety and author).
29
Herbal substances are a diverse range of botanical materials including leaves, herbs, roots,
flowers, seeds, bark etc.A comprehensive specification must be developed for each herbal
substance even if the starting material for the manufacture of the herbal preparation . In the
case of fatty or essential oils used as active substances of herbal medicinal products a
specification for the herbal is required unless justified. 25
 Identification Tests:
 Foreign matter:
Foreign matter in herbal drugs consists of either parts of medicinal plant other than those
named with specified limit; or it may be any organism, part or product or an organism. It may
also include mineral admixtures not adhering to the medicinal plant material e.g. soil, stones,
dust etc.Medicinal plant material should be entirely free from visible sign of any
contamination.11
o Sampling :
To prepare a pooled sample for herbal drugs is very difficult as most of the foreign matters
are adhered to the medicinal plant material, which are intrinsically non-uniform. That is why
it is crucial that the size of the sample should be sufficiently large to be considered as a true
representative. In the case of whole drug, a weighed quantity (50-500gm) according to the
type of the drug is taken as sample.
o Procedure:
The specific quantity of plant material as mentioned below is spread on a thin layer of paper.
To sort onto different groups of foreign matter it has to be examined either by visual
inspection or by using magnifying lenses (6x or 10x) and the foreign matter are picked out
and the percentage is recorded. The remainder of herbal drug sample is passed through 250
mesh sieve to make it free from dust, which is regarded as mineral admixture. The content of
each group of foreign matter should be calculated in gram per 100gm of air dried sample.
30
Unless otherwise specified the quantities of samples to be taken into account to determine the
foreign matters of any herbal drugs as specified WHO are as follows:
Leaves, flowers, seeds and fruits - 250 gm
Roots, rhizomes and barks - 500 gm
Cut medicinal plant material - 50 gm
 Total ash:
Ashing involves an oxidation of the components of the product. A high ash value is
indicative of contamination, substitution, adulteration or carelessness in preparing the crude
drug for marketing. Total ash is designed to measure the total amount of material produced
after complete incineration of the ground drug at as low temperature as possible (about
450°C) to remove all the carbons. At higher temperature, the alkali chloride may be volatile
and may be lost by this process. The total ash usually consists of carbonates, phosphates,
silicates and silica which include both physiological ash - which is derived from the plant
tissue itself and non-physiological ash - which is the residue of the adhering material to the
plant surface, e.g., sand and soil.11
While determining the total ash very high temperature (>600°C) may result in the conversion
of carbonates to oxides. I n that cases re-carbonation may be done by treatment of the ash
with a solution of ammonium carbonate and further re drying to constant weight which give
the carbonated ash. The similar treatment with dilute H2SO4 results in sulphated as where the
oxides are converted to sulphates. When the same treatment is done by dilute HN03 results in
nitrated ash. As recommended by the World Health Organization the total ash can be
determined by the following procedure:
Place about 2-4 g of ground air dried material, accurately weighed in a previously ignited and
tared crucible of platinum or silica. Spread the material in an even layer and ignite it by
gradually increasing the heat to 500-600°C until it is white, indicating the absence of
carbon.11
Cool in a dessicator and weigh. If carbon free ash cannot be obtained in this manner, cool;
the crucible and moisten the residue with about 2 ml of water or a saturated solution of
31
ammonium nitrate. Dry on a water bath, then on a hot plate and ignite to constant weight.
Allow the residue to cool in a suitable dessicator for 30 minutes, and then weigh without
delay. Calculate the content of total ash in mg/g of the air dried material. Indian
Pharmacopoeia 1996 prescribes suitable method for the determination of ash values. Method
I is for crude vegetable drugs and Method II for other substances:
o Method I
Unless otherwise stated in the individual monographs, weigh accurately 2 to 3 g of the air
dried crude drug in the tared platinum or silica dish and incinerate at a temperature not
exceeding 450°C until free from carbon, cool and weigh. If a carbon-free ash cannot be
obtained in this way, exhaust the charred mass with hot water, collect the residue on an ash
less filter paper, incinerate the residue and filter paper until the ash is white or nearly so.
Calculate the percentage of ash with reference to the air-dried drug.
o Method II
Heat a silica or platinum crucible to red heat for 30 minutes; allow cooling in a dessicator
and weighing. Unless otherwise specified in the individual monograph, weigh accurately
about 1g of the substance being examined and evenly distribute it in the crucible. Dry at
100°C to 105°C for 1 hour and ignite to constant weight in a muffle furnace at 600° +
25°C. Allow the crucible to cool in a dessicator after each ignition. The material should not
catch fire at any time during the procedure. If after prolonged ignition a carbon free ash
cannot be obtained, proceed as directed in method I. Ignite to constant weight. Calculate
the percentage of ash with reference to the air-dried substance.
 Acid Insoluble Ash

Boil the ash obtained for 5 minutes with 25 ml of dilute hydrochloric acid, collect the
insoluble matter in a Gooch crucible or on an ashless filter paper, wash with hot water and
ignite to constant weight. Calculate the percentage of acid insoluble ash with reference to the
air dried drug.11
32
 Water Soluble Ash

Boil the ash for 5 minutes with 25 ml of water, collect insoluble matter in a Gooch crucible
or on an ashless filter paper, wash with hot water, and ignite for 15 minutes at a temperature
not exceeding 450°c. Subs tract the weight of the insoluble matter from the weight of the ash,
the difference in weight represents the water soluble ash. Calculate the percentage of water
soluble ash with reference to the air dry.11
 Water Soluble Extractive
This method determines the amount of active constituents in a given amount of medicinal
plant material when extracted with solvents. It is employed for that material for which no
chemical or biological assay method exist. As mentioned in different official books (Indian
Pharmacopoeia 1996, British Pharmacopoeia 1980, British Herbal Pharmacopoeia.1990 etc.),
the determination-of water soluble and alcohol soluble extractives, is used as a means of
evaluating crude drugs which are not readily estimated by other means.11
Method I
5 g of the air-dried drug, coarsely powdered have to be macerated with 100 ml of water
closed flask for 24 hours, shaking frequently during the first 6 hours and allowing to stand
for 18 hours. Thereafter, filter rapidly taking precautions against loss of water, evaporate 25
ml of the filtrate to dryness in a tared flat-bottomed shallow dish, dry at 105°C and weigh.
The percentage of water-soluble extractive with reference to the air dried drug has to be
calculated.
oMethod II
Add 5 g of powdered drug to 50 ml of water at 80°C in a stoppered flask. Shake well and
allow to stand for 10 minutes. Cool, add 2 g of kieselguhr and filter. Transfer 5 ml of the
filtrate to a tared evaporating dish 7.5 cm in diameter. Evaporate the solvent on a water bath,
continue drying for 30 minutes, finally dry in a steam oven for 2 hours and weigh the residue.
Calculate the percentage of water-soluble extractive with reference to the air-dried drug.
33
 Alcohol Soluble Extractive
The alcohol soluble extractive value is also indicative for the same purpose as water soluble
extractive value. The solvent strength of alcohol varies from 20 - 95 % v/v. The solvent
strength has to be chosen depending on the nature of drugs to be extracted. The extractive
value varies depending on the strength of alcohol used for extraction, e.g. ginger when
extracted with 90% alcohol gives an alcohol soluble extractive value of approximately 4.5%
vlv, which-includes the oil and resins present in it. In case of rhubarb, 45% vlv alcohol
strength is suitable to extract the anthraquinone present in it. With reference to Indian
Pharmacopoeia 1996, the ethanol soluble extractive can be determined as follows:
Macerate 5 g of the air dried drug, coarsely powdered, with 100 ml of alcohol of the
specified strength in a closed flask for 24 hours, shaking frequently during six hours and
allowing standing for eighteen hours. Filter rapidly, taking precautions against loss of
solvent, evaporate 25 ml of filtrate to dryness in a tared flat bottomed shallow dish, and dry
at 105°, to constant weight and weigh. Calculate the percentage of alcohol soluble extractive
with reference to the air dried drug.11,25
 Water Soluble Extractive
Proceed as directed for the determination of Alcohol soluble extractive, using chloroform
water instead of ethanol.
 Ether Soluble Extractive (Fixed Oil Content)
Transfer the suitably weighed quantity of the air dried, crushed drug to an extraction thimble,
extract with solvent ether (or petroleum ether, b.p. 40° to 60°) in a continuous extraction
apparatus (Soxhlet) for 6 hours. Filter the extract quantitatively into a tared evaporating dish
34
and evaporate off the solvent on a water bath. Dry the residue at 105° to constant weight.
Calculate the percentage of ether soluble extractive with reference to the air dried drug.
In the determination of all extractive values, the percentage has to be determined with respect
to the air-dried material where the determination of moisture content is important. This is in
contrast to some of the assay procedures on plant drugs, where, if the drug has to be dried
before extraction apparatus is made for the loss on drying and the constituent content is
calculated with reference to the un-dried or fresh drug. 11
 Moisture content:
Moisture is an inevitable component of crude drugs, which must be eliminated as far as
practicable. The preparation of crude drug from the harvested drug plants involves cleaning
or garbling to remove soil or other extraneous material followed by drying which plays a
very important role in the quality as well as purity of the material. The objective of drying
fresh material is:
℘ To aid in their preservation
℘ To "fix" their constituents, i.e., to check enzymatic or hydrolytic reactions that
might alter the chemical composition of the drug
℘ To facilitate subsequent comminution (grinding into a powder) and
℘ To reduce their weight and bulk
Insufficient drying favors spoilage by molds and bacteria and makes possible the enzymatic
destruction of active principles. The moisture requirements for the active growth of some of
the common molds and bacteria that may be found in or on drugs are relatively low.
Therefore, the drying process should reduce the moisture content of the drug below this
critical, or threshold level. Since the moisture requirements for enzymatic activity and that
which microorganisms demand, vary not only with the species, but also with other
environmental factors (e.g., temperature, oxygen and carbon dioxide tension, light etc.). It is
difficult to state a precise upper limit of moisture that can be permitted in crude drugs. The
USP and the NF make no commitment in this regard in most cases. However, most drugs
35
may be stored safely if the moisture content is reduced to 6 per cent or less. A notable
exception is agar, for which USP permits as much as 20 per cent moisture.
Not only is the ultimate dryness of the drug is important, equally important is the rate at
which the moisture is removed and the conditions under which it is removed. If the rate is too
slow, much spoilage may occur before the drying process is completed. Therefore, in
general, drying should be accomplished as rapidly as is possible with good practice. The
duration of the drying process varies from a few hours to several weeks, depending on the
water content and other features of the drugs. Consideration of the time during which an
elevated drying temperature is maintained is important, because destructive enzymatic
reactions are accelerated by increasing the temperature, although the net effect of most such
reactions commonly encountered in the preparation of crude drugs is accelerated only up to
approximately 45°C. But higher temperatures shorten the time required for drying, and thus
the time during which destructive reaction can occur also. The methods employed for drying
are variable in detail, but they may be classified as spontaneous or as artificial. Artificial
methods may be physical, which involves the use of elevated temperature and/or decreased
pressure (vacuum), or the use of radiation of infrared or radio-frequency wave lengths; or
they may be chemical, which involve use of the desiccants.
The extractive values as described under section 9.2 determine the presence of specific
component or group of specific components or contaminants in a plant drug. The moisture
content of many crude drugs may be ascertained by the simple physical process of
evaporation. A weighed sample of the crude herb is dried at 100°C and weighed periodical~
until no more than 0.25 percent is lost in one hour's drying. The total weight lost is expressed
as a percentage of the initial weight of the sample; this figure is the moisture content of the
sample. The residual moisture (if any) which cannot be driven off in this way is called
"bound" water. A high-speed mill or other devices that are likely to create excessive heat I
from friction should not be used for grinding or cutting samples intended for moisture
determination.
It is doubtful whether moisture can truly be classified with these types of constituents an
contaminants, but as the procedure for the determination of moisture is analogous with the
extraction methods described, it is included in this section. Excess moisture in a sample
36
suggests not only that the purchaser could be paying a high price for unwanted water, but
also that the drug has been incorrectly prepared, or, subsequent to preparation, has been
incorrectly stored. Excess moisture can result in the breakdown of important constituents by
enzymatic activity and may encourage the growth of -yeast and fungi during storage. The
results in either case will be the eventual rejection of the drug as an unsuitable material.
Moisture content limits are stated in the pharmacopoeial monographs on many drugs. Other
drugs have no limit statement expressed, the limit, by inference, being that the drug should be
air-dried. This only requires that the drug has reached equilibrium with the surrounding
humidity, which will naturally vary according to the location of the material. The
significance of this standard is demonstrated in the exercises on the moisture content of
starch and digitalis.
Methods of determination of moisture content include the loss on drying, the volumetric
azeotropic distillation method and the titrimetric Karl Fischer method. Which method is to
be applied depends on the nature of the drug and its constituents.
The test for loss on drying determines both water and volatile matter in the crude drug. It can
be carried out either by heating at 1 00°C-1 05°C or in a desiccator’s over phosphorous pent
oxide under atmospheric or reduced pressure at room temperature for specific period of time.
The second method is especially useful for those materials that melt to a sticky mass at
elevated temperature.11
 Particle size:
For some herbal substances intended for use in herbal teas or solid herbal medicinal products,
particle size can have a significant effect dissolution rates, bioavailability, and/or stability. In
such instances, testing for particle size distribution should be carried out using an appropriate
procedure, and acceptances criteria should be provided. Particle size can also be affected the
disintegration time of solid dosage forms.
37
 Contaminants:
i) Inorganic impurities /Toxic metals:

The need for inclusion of tests and acceptance criteria for inorganic impurities should be
studied during development and based on knowledge of the plant species, its cultivation and
the manufacturing process.11
ii) Determination of arsenic:

The medicinal plant materials can be contaminated with arsenic and heavy metals which can
be attributed to many causes including environmental pollution and traces of pesticides. As
these components even in trace amounts are dangerous, they have to be removed from the
herbal drugs. Limit tests for these materials have been prescribed in almost all the
Pharmacopoeia through out the world. As prescribed by WHO the following procedures have
been recommended for their respective limit tests 11
Limit Test for Arsenic:
The amount of arsenic in the medicinal plant material is estimated by matching the depth of
color with that of a standard stain. The limit test can be accomplished by using the following
procedures.
38
Preparation of the sample by acid digestion:
Place 3S-70 g of coarsely ground material, accurately weighed, in a kjeldahl flask, capacity
800-1000 ml. Add 10-25 ml of water and 25-50 ml of nitric acid (-1000 g/l) and then
carefully add 20 ml of sulfuric acid (-1760g/l), drop by drop, until all the organic matter is
destroyed.
This is achieved when no further darkening of the solution is observed with continued
heating, and a clear solution with copious vapors of sulfur trioxide is obtained. Cool, and add
75 ml of water and 25 ml of ammonium oxalate (25g/l). Heat again until sulfur trioxide
vapors develop. Cool, transfer with the help of water to a 250 ml volumetric flask, and dilute
to volume with water(1).
Apparatus
A suitable type of apparatus is constructed as follows. A wide mouthed bottle of about 120ml
capacity is fitted with a rubber bung through which passes a glass tube. The latter, made from
ordinary glass tubing, has a total length of about 200 mm and an internal diameter 01 exactly
6.5 mm (external diameter about 8 mm). The lower end of -the tube is drawn out to an
internal diameter of about 1 mm, and there is a hole not less than 2 mm in diameter below the
side of the tube, near the constricted part. The tube is positioned so that when the bottle
contains 70 ml of liquid the constricted end is above the surface of the liquid and the hole in
the side is below the bottom of the tube, with slightly rounded-off edges. One of two rubber
bungs (about 25 mm x 25 mm), each with a central hole of exactly 6.5 mm diameter, is fitted
at the upper end of the tube. The other bung is fitted with a piece of glass tube about 3 mm
long and with an internal diameter of exactly 6.5 mm and with a similar ground surface. One
end of each of the tubes is flush with the larger end of the bungs, so that when these ends are
held tightly together with a rubber band or a spring clip, the openings of the two tubes meet
to form a true tube. Alternatively, the two bungs may be replaced by any suitable
construction satisfying the conditions described in the test.11
39
Method
Moisten some cotton-wool with lead acetate (80 g/I), allow drying, and lightly packing into
the tube which fits into wide-mouthed bottle to not less than 25 mm from the top. Between
the flat surfaces of the tubes, place a piece of mercuric bromide paper that is large enough to
cover their openings \ -15 mm x 15 mm). The mercuric bromide paper can be fitted byan1
other means provided that:
The whole of the evolved gas passes through the paper
The portion of the paper in contact with the gas is a circle 6.5 mm in diameter The paper is
protected from sunlight during the test
Place an aliquot (25-50 ml) of the solution being tested, prepared as described above, in the
wide-mouthed bottle. Add 1 g of potassium iodide ASR and 10 g of granulated zinc ASR and
place the prepared glass tube assembly quickly in position. Allow the reaction to proceed for
40 minutes. Compare any yellow stain that is in a similar manner with a known quantity of
dilute arsenic As TS. Examine the test and standard stains without delay in daylight; the
stains fade with time.
The most suitable temperature for carrying out the test is generally about 40°C but, as the
rate of evolution of the gas varies somewhat with different batches of granulated zinc ASR,
the temperature may have to be adjusted to obtain an even evaluation of gas. The reaction
may be accelerated by placing the apparatus on a warm surface, care being taken to ensure
that the mercuric bromide paper remains dry throughout. Between successive tests, the tube
must be washed with hydrochloric acid (- 250g/l) As TS, rinsed with water and dried.(1)
40
Limit Test for Cadmium and Lead
The method of determination is left to the analyst. Nevertheless the determination must be
consistent and sensitive enough to allow comparison with a reference material. The
procedure for the determination of the same as recommended by the WHO is as follows:11
Apparatus
The equipment consists of a digestion vessel, consisting of a vitreous silica crucible (DIN
12904), "tall form", height 62 mm, diameter 50 mm, capacity 75 ml, with a vitreous silica
cover.
Materials used are:
Digestion mixture: 2 parts by weight of nitric acid (-1 000g/1) TS and 1 part by weight of
perchloric acid (-1170g/I).
Reference materials: olive leaves (Olea europaea) and hay powder.
Clean scrupulously with nitric acid (-1000g/l) the digestion vessel and all other equipment to
be used for the determination, rinse thoroughly several times with water and dry at 120°C.
Preparation of the sample:
For the wet digestion method in an open system, place 200-250 mg of air-dried plant
material, accurately weighed, finally cut and homogeneously mixed, into a cleaned silica
crucible. Add 1 ml of the digestion mixture, cover the crucible without exerting pressure and
place it in an oven with a controlled temperature and time regulator (computer-controlled, if
available). Heat slowly to 1OQoC and maintain at this temperature for up to 3 hours, then
heat to 120°C and maintain at this temperature for 2 hours. Raise the temperature very slowly
to 240°C, avoiding losses due to possible violent reactions especially in the temperature
range of 160-200°C, and maintain at this temperature for 4 hours. Dissolve the remaining dry
inorganic residue in 2.5 ml of nitric acid (-1000g/l) and use for the determination of heavy
metals. Every sample should be tested in parallel with a blank.
41
Method
The contents of lead and cadmium may be determined by inverse voltametry or by atomic
absorption spectrophotometry. The following maximum amounts in dried plant materials,
which are based on the ADI values, are proposed:
Lead, 10 mg/kg
Cadmium, 0.3 mg/kg
Microbial limits:
There may be a need to specify the total count of aerobic micro-organisms, the total count of
yeasts and moulds, and the absence of specific objectionable bacteria. The section contains
tests for the determination of the number of replicable microorganisms and for the
demonstration of the absence of certain species of microbes in all types of pharmaceutical
products and minerals, from crude starting materials to finished products. Strict adherence to
aseptic working conditions must be ensured in the preparation and execution of the tests.
Unless stated otherwise, ‘incubation’ means the storage of the material in an incubator at 30-
35 C for 24-48 hours. The word ‘growth’ is used in the sense of expressing the presence and
expected multiplication of live micro - organisms.11
42
Limits of Microbial load:
Microbes Plant material for topical Plant material for internal

use Per gram use per gram
Aerobic Bacteria 107 105
Yeast and moulds 104 103
Escherichia coli 102 10
Other enterobacteria 104 103
Salmonella None None
Mycotoxins
The potential for mycotoxins contamination should be fully considered. Where necessary
suitable validated methods should be used to control potential mycotoxins and the acceptance
criteria should be justified.
Pesticides, fumigation agents etc

Microbiological contamination and foreign materials are important quality criteria in the
testing of medicinal plants. As with any other product from agricultural or wild sources,
medicinal plants can be contaminated by organic substances of natural or synthetic origin ,
such as insects, micro-organisms, e.g. fungi and their mycotoxins , radioactive materials ,
fumigation residues and plant protection substances, i.e. pesticides.
43
Pesticides are simple substances or mixtures used to eliminate undesirable vegetable and
animal life in agricultural and urban ecosystems. Owing to the great variability in plant
chemical composition that results from factors to which plants are exposed during their
growth, storage and the different stages of manipulation, characterization and /or
standardization of phytopharmaceuticals are necessary. Standardization of herbal
preparations should allow the knowledge of their composition and prevent, or at least make
less likely, the consumption of drugs of questionable quality. Depending on the type of
preparation, organoleptic features, moisture and ash content, physical properties and
adulterants are check to confirm identity and determine purity.11
Other appropriate tests:
Swelling Index:
The dried ripe seeds of Plantago ovata, P. psylium, P. arenaria, P. indica etc. contain
mucilage in the epidermis of the testa. The seeds of such types of plant may be evaluated by
measuring the volume of mucilage produced in 24 hours from 1 g of the seeds. This
evaluation procedure is termed as swelling factor. The swelling index is the volume in ml
taken up by the swelling of 1 g of plant material under specified conditions. Its determination
is based on the addition of water or a swelling agent as specified in the test procedure for
each individual plant material (either whole, cut or pulverized). Using a glass-stoppered
measuring cylinder, the material is shaken repeatedly for 1 hour and then allowed to stand for
a required period of time. The volume of the mixture (in ml) is then read. The mixture of
whole plant material with the swelling agent is easy to achieve, but cut or pulverized material
requires vigorous shaking at specified intervals to, ensure even distribution of the material in
the swelling agent. As this constitutes a valid parameter for the evaluation of the
mucilaginous plant, the W!-IO has prescribed the following method for the determination of
the swelling index.11
44
Recommended Procedure for the Determination of Swelling Index

No fewer than three determinations for any given material have to be carried out
simultaneously. The specified quantity of the plant material concerned is introduced,
previously reduced to the required fineness and accurately weighed, into a 25 ml glass
stoppered measuring cylinder. The internal diameter of the cylinder should be about 16 mm,
the length of the graduated portion about 125 mm, marked in 0.2 ml divisions from 0 to 25
ml in an upwards direction. Unless otherwise indicated in the test procedure, 25 ml of water
is to be added. The mixture is shaken thoroughly every 10 minutes for 1 hour. Allow to stand
for 3 hours at room temperature or as specified. The volume (in ml) has to be measured
which is occupied by the plant material, including any sticky mucilage. The mean value of
the individual determinations is calculated relating to 1 g of plant material.11
Assay:
In the case of herbal substances with constituents of known therapeutic activity or with active
markers, assays of their content are required with details of the analytical procedures. Where
possible, a specific, stability- indicating procedure should include determining the content of
the herbal substance. In cases where use of non –specific assays justified, other supporting
analytical procedures may be used to achieve overall specificity, if required.
Foaming Index:-
The saponins are high molecular weight containing phytoconstituents having the detergent
activity. Saponins are mostly characterized based on their frothing property. Medicinal plants
of different groups, especially those derived from the families Caryophyllaceae, Araliaceae,
Sapindaceae, Primulaceae, and Dioscoreaceae contain saponins. 11
Recommended procedures for foaming index determination

Reduce about 1gm of the plant material to a coarse powder (sieve no. 1250) , weigh
accurately and transfer to a 500ml conical flask containing 100ml of boiling water. Maintain
45
at moderate boiling for 30min. Cool and filter into a 100ml volumetric flask and add
sufficient water through the filter to dilute to volume. Pour the decoction in to ten stoppered
test tubes (height 16cm , diameter 16mm) in successive portion in 1ml ,2ml, 3ml and adjust
the volume of the liquid in each tube with water to 10ml. Stopper the tubes and shake them
in a length wise motion for 15sec, two shakes per second. Allow to stand for 15min and
measure the height of the foam.
Calculate the foaming index by using the following formula: -
1000 / A
Where, A= the volume in ml of the decoction used for pre paring the dilution in the tube
where foaming to a height of 1cms is observed.
46
Herbal preparations
They are obtained by subjecting herbal substances to treatments such as extraction,
distillation, expression, fractionation, purification, concentration or fermentation. These
include comminuted or powdered herbal substances, tinctures, extracts, essential oils,
expressed juices and processed excudes.
Identification tests:
o Water content
o Residual Solvents
o Inorganic impurities, toxic metals
o Microbial Limits
o Mycotoxins
o Pesticides, Fumigation agents,etc
o Assay
47
Herbal medicinal products

These are any medicinal product, exclusively containing as active substances one or more
herbal substances or one or more herbal preparation, or one or more herbal substances in
combination with one or more such herbal preparations.
The tests and acceptance should be included for particular herbal medicinal products. The
specific dosage forms addressed include solid oral herbal medicinal products.
Tablet (Coated and uncoated) and hard capsules:

One or more of these tests may also be applicable to soft capsule and granules.
a) Disintegration :
The first important step toward solution is break down of the tablet into smaller particles, a
process known as disintegration.
Disintegration Test For Tablets
Apparatus
(a) A rigid basket – rack assembly supporting six cylindrical glass tubes, 77.5+ -2.5 mm
long, 21.5mm in internal diameter and with a wall thickness of about 2mm.
(b) The tubes are held vertically by two superimposed transparent plastic plates, 90mm in
diameter and 6m thick, perforated by six holes having the same diameters as the
tubes. The holes are equidistant from the centre of the plate and are equally spaced
from one another. Attached to the under side of the lower plate is a piece of woven
gauze made from stainless steel wire 635micro meter in diameter and having nominal
mesh apertures of 2.00mm The upper plate is covered with a stainless steel disc
perforated by six holes, each about 22mm in diameter, which fits over the tubes and
holds them between the plastic plates. The holes coincide with those of the upper
plastic plate and the upper open ends of the glass tubes.
48
(c) The plates are held rigidly in position and 7705mm apart by vertical metal rods at the
periphery and a metal enable the assembly to be attached to a mechanical device
capable of raising and lowering it smoothly at a constant frequency of between 28
&32 cycles per minute through a distance of 50&60 mm.
(d) A cylindrical disc for each tube, each 20.7+- o.15mm in diameter & 9.5+-0.15mm
thick, made of transparent plastic with relative density of 1.18 to 1.20, & pierced with
5holes, each of 2mm in diameter, 1 in the centre & the other 4 spaced equally on the
circle of radius 6mm from the centre of the disc.
(e) The assembly is suspended in the liquid medium in a suitable vessel, preferably a
1000ml beaker.
(f) A thermostatic arrangement for heating the liquid & maintaining the temperature at
37o +-2o.
Method
Unless otherwise stated in the individual monograph, introduced 1tab into each
tube, add a disc to each tube. Suspend the assembly in the beaker containing the
specified liquid and operate the apparatus for the specified time. Remove the
assembly from the liquid. The tablet pass the test if all of them are disintegrated.
If 1or2 tab. failed to disintegrate repeat the test on 12 additional tab; not less
than 16 of the total of 18 tab. Tested disintegrate
b) Dissolution:
The original rationale for using tablet disintegration tests was the fact that as the tablet breaks
down into smaller particles, it offers a greater surface area to the dissolving media and
therefore must be related to the availability of the drug to the body.
Dissolution Test For Tablets
Apparatus 1
An assembly consisting of the following:
49
(a) A cylindrical vessel, A, made of borosilicate glass or any other suitable transparent
material, with a hemispherical bottom and with a nominal capacity of 1000 ml . The
vessel has a flanged upper rim and is fitted with a lid that has a number of openings,
one of which is central.
(b) A motor with a speed regulator capable of maintaining the speed of rotation of the
paddle with in 4% of that specified in the individual monograph. The motor is fitted
with a stirring element which consists of a drive shaft and blade forming a paddle, B
(c) A water-bath set to maintain the dissolution medium at 36.5o to 37.5o . The bath liquid
is kept in constant and smooth motion during the test. The vessel is securely clamped
in the water-Bath in such a way that the displacement vibration from other
equipment.
Method :-
Introduce the stated volume of the dissolution medium, free from dissolved air, in to the
vessel of the apparatus. Warm the dissolution medium to between 36.5o and 37.5o.Unless
otherwise stated use one tablet . When Apparatus 1 is used, allow the tablet to sink to the
bottom of the vessel prior to the rotation of the paddle. A suitable device such as a wire
or glass helix may be used to keep horizontal at the bottom of the vessel tablets that
would otherwise float. Care should be taken to ensure that air bubbles are excluded from
the surface of the tablet . Perform the analysis as directed in the individual monograph.
Repeat the whole operation five times. Where two or more tablets are directed to be
placed together in the apparatus, carry out six replicate tests.
For each of the tablet tested, calculate the amount of dissolved active ingredient in the
solution as a percentage of the stated amount.
c) Hardness:
Tablets require a certain amount of strength, or hardness and resistance to friability, to
withstand mechanical shocks of handling in manufacture, packaging, and shipping.
Historically, the strength of a tablet was determined by breaking it between the second and
third fingers with the thumb acting as a fulcrum. If there was a sharp snap, the tablet was
deemed to have acceptable strength. Nowadays diametric compression tests are applied by
using following instruments:14
50
Monsanto tester,
Strong-Cobb tester,
Pfizer tester,
Erweka tester etc.
The Monsanto hardness tester consists of a barrel containing a compressible spring held
between two plungers. The lower plunger is placed in contact with the tablet, and a zero
reading is taken. The upper plunger is then forced against a spring by turning a treaded bolt
until the tablet fractures. The force of fracture is recorded, and the zero force reading is
deducted from it.
The Strong –Cobb tester was developed about 20 years later. The original design employed a
plunger activated by pumping a lever arm, which forces an anvil against a stationary platform
by hydraulic pressure. The force required to fracture the tablet is read from a hydraulic
gauge.
The Pfizer tester was developed and made available to the industry. This tester operates on
the same mechanical principle as a pair of pliers. As the plier’s handles are squeezed, the
tablet is compressed between a holding anvil and a piston connected to a direct force reading
gauge. 14
d) Friability:
The tablet friability can be determined by Roche friabilator. The tablets are subjected to the
combined effects of abrasion and shock by utilizing a plastic chamber that revolves at 25
rpm, dropping the tablets at a distance of 6 inches with each revolution. Normally, a
preweighed tablet sample is placed in the friabilator, which is then operated for 100
revolutions. The tablets are then dusted and reweighed. Loss of tablet material less than 0.5
to 1.0% of the tablet weight is accepted.14
e) Weight Variation:
As per USP weight variation test, 20 tablets are weighed individually; average weight is
calculated, followed by comparing the individual tablet weights to the average. The tablets
51
meet the USP test if not more than 2 tablets are outside the percentage limit and if no tablet
differs by more than 2 times the percentage limit.14
Table: Weight variation tolerances for uncoated tablets:
S.No. Average weight of tablets(mg) Max. % difference allowed

1. 130 or less 10
2. 130- 324 7.5
3. More than 324 5
52
f) Moisture content:
Moisture is an inevitable component of crude drugs, which must be eliminated as far as
practicable. The preparation of crude drug from the harvested drug plants involves cleaning
or garbling to remove soil or other extraneous material followed by drying which plays a
very important role in the quality as well as purity of the material. The objective of drying
11
freshmaterial is:
℘ To aid in their preservation
℘ To "fix" their constituents, i.e., to check enzymatic or hydrolytic reactions that
might alter the chemical composition of the drug
℘ To facilitate subsequent comminution (grinding into a powder) and
℘ To reduce their weight and bulk
g) Uniformity of dosage units:

This term include both uniformity of content and uniformity of mass.
h) Microbial limits
Microbial limit testing is seen as an attribute of good manufacturing practice, as well as of
quality assurance. It is advisable to test the herbal product unless its components are tested
before manufacture and the manufacturing process is known, through validation studies, not
to carry a significant risk of microbial contamination.
Where appropriate, acceptance criteria should be set for the total count of aerobic micro-
organisms, the total count of yeasts and moulds, and the absence of specific objectionable
bacteria (e.g., Staphylococcus aureus, Escherichia coli, Salmonella, pseudomonas).Counts
should be determined using phamacopoeial or other validated procedures, and a sampling
frequency or time point in manufacture which is justified by data and experience. With
acceptable scientific justification, it may be possible to omit microbial limit testing for solid
dosage forms.11
53
Oral liquids:
One or more of the following specific test will normally be applicable to oral liquids and to
powders intended for reconstitution as oral liquids.22
i) Uniformity of dosage units:

This term include both uniformity of content and uniformity of mass. Generally, acceptance
criteria should be set for weight variation, fill volume, and/or uniformity of fill.
Pharmacopoeial procedures should be used
If appropriate, tests may be performed as in-process controls; however, the acceptance
criteria should be included in the specification. This concept may be applied to both single-
dose and multiple dose packages.
The dosage unit is considered to be the typical dose taken by the patient. If the actual unit as
taken by patient, is controlled, it may either be measured directly or calculated, based on the
total measured weight or volume of drug, divided by the total number of doses expected. If
dispensing equipment (such as medicine droppers or droppers tips for bottles) is an integral
part of packaging, this equipment should be used to measure the dose. Otherwise, a standard
volume measure should be used. The dispensing equipment to be used is normally
determined during development.
For powders for reconstitution, uniformity of mass testing is generally considered
acceptable.11,14
ii) pH:
Acceptance criteria for pH should be provided where applicable and the proposed range
justified.
54
iii) Microbial limits:

Microbial limit testing is seen as an attribute of good manufacturing practice, as well as of
quality assurance. It is advisable to test the herbal product unless its components are tested
before manufacture and the manufacturing process is known, through validation studies, not
to carry a significant risk of microbial contamination.
Where appropriate, acceptance criteria should be set for the total count of aerobic micro-
organisms, the total count of yeasts and moulds, and the absence of specific objectionable
bacteria (e.g., Staphylococcus aureus, Escherichia coli, Salmonella, pseudomonas).Counts
should be determined using phamacopoeial or other validated procedures, and a sampling
frequency or time point in manufacture which is justified by data and experience. With
acceptable scientific justification, it may be possible to omit microbial limit testing for solid
dosage forms.
iv) Antimicrobial Preservative Content:
For oral liquids needing an antimicrobial preservative, acceptance criteria for preservative
content must be stated. These criteria should be based on the levels necessary to maintain
microbiological product quality throughout the shelf-life.
Releasing testing for antimicrobial preservative content should normally performed. Under
certain circumstances, in-process testing may suffice in lieu of release testing. When
acceptance criteria hen antimicrobial preservative content testing is performed as an in-
process test, the acceptance criteria should remain part of the specification.
Antimicrobial preservative effectiveness should be demonstrated during development, during

scale-up, and through shelf-life.23,24
55
v) Antioxidant preservative content:
Releasing testing for antioxidant content should normally performed. Under certain
circumstances, where justified by development and stability data, shelf –life testing may be
unnecessary, and in-process testing may suffice in lieu of release testing. When accept
antioxidant content testing is performed as an in-process test, the acceptance criteria should
remain part of the specification. If only release testing is performed, this decision should be
reinvestigated whenever either the manufacturing procedure or the container/closure system
changes.
vi) Extractables:
Generally, where development and stability data show no significant evidence of extractable
from the container/closure, elimination of this test may be proposed. This should be
reinvestigated if the container/closure system changes.
Where data demonstrate the need , tests and acceptance criteria for extractable from the
container-closure system components ( e.g. , rubber stopper , cap liner , plastic bottles, etc.)
are considered appropriate for oral solutions packaged in non-glass system, or in glass
containers with non-glass closure. The container/closure components should be listed, and
data collected for these components as early in the development process as possible. 23,24
vii) Alcohol content:
Where it is declared quantitatively on the label in accordance with pertinent regulations, the
alcohol content should be specified11
56
viii) Dissolution:
In addition to the attributes recommended immediately above it may be appropriate (e.g.

where constituents of the herbal substance or herbal preparation are sparingly soluble) to
include dissolution testing and acceptance criteria for oral suspensions and dry powder
products for resuspension.
Dissolution testing may be performed as in-process test, or as a release test, depending on its
relevance to product performance. The discussion of dissolution for solid dosage forms, and
of particle size distribution, should also be considered.14
ix) Particle Size Distribution:
Quantitative acceptance criteria and a procedure fort determination of particle Size

Distribution may be appropriate for oral suspensions
Particle size distribution testing may be performed as in-process test, or as a release test,
depending on its relevance to product performance. If these products have been demonstrated
during development to have consistently rapid drug release characteristics, exclusion of a
particle size distribution test from the specification may be proposed.
Particle size distribution testing may also be proposed in place of dissolution testing;
justification should be provided. The acceptance criteria should include acceptable Particle
size distribution in terms of the percentage of total particle size ranges. The mean, upper,
and/or lower particle size limits should be well defined.14
57
x) Redispersibility:
For oral suspensions, which settle on storage (produce sediment) acceptance criteria for
redispersibility may be appropriate. Shaking may be an appropriate test. The procedure
(mechanical or manual) should be indicated. Time required to achieve resuspension by the
indicated procedures should be clearly defined. Data generated during product development
may be sufficient to justify skip lot testing, or elimination of this attribute from the
specification.14
xi) Rheological Properties:
For relatively viscous solutions or suspensions, it may be appropriate to include rheological

Properties (viscosity) in the specification. The test and acceptance criteria should be stated.
Data generated during product development may be sufficient to justify skip lot testing, or
elimination of this attribute from the specification.14
xii) Specific Gravity:
The specific gravity of a liquid is the weight of a given volume of the liquid at 25°
Compared with the weight of an equal volume of water at the same temperature, all
Weighing being taken in the air.11
Method:
Proceed as described under Wt. per ml. Obtain the specific gravity of the liquid by
Dividing the weight of the liquid contained in the pyknometer by the weight of the water
Contained, both determined at 25° unless otherwise directed in the individual
Monograph.(1)
58
Xiii) Reconstitution Time:
Acceptance criteria for reconstitution Time be provided for dry powder products, which
require reconstitution. The choice of diluents should be justified. Data generated during
product development may be sufficient to justify skip lot testing, or elimination of this
attribute from the specification.
xiii) Water Content:
For oral products requiring reconstitution, a test and acceptance criterion for water content
should be proposed when an appropriate. Loss on drying is generally considered sufficient if
the effect of absorbed moisture vs. water of hydration has been adequately characterized
during the development of the product. In certain cases (e.g. essential-oil containing
preparations) a more specific procedure (e.g., Karl Fischer titration) is required.11
59
PHYSICAL QUALITY ASSURANCE

Quality assurance of phyto-pharmceuticals products has so far been discussed solely from the
chemical and physiological point of view. The physical quality however plays an equally
important role for the manufacturer and processor of plant extracts. Without the addition of
suitable adjuvant substances, many plant extracts occur in a form, which makes further
processing considerably more difficult, often even impossible. Hence , extracts of Crataegus
fruits, Curcuma extracts and many others cannot be processed to more manageable dry
products either by roller, belt or spray drying. One particular example is the male fern
extract, which is produced as a solvent free thin extract. In all such cases the manufacturer
cannot handle this without consideration addition adjuvant substances (Newall, 1996) .
Before drying therefore, a proportion of Aerosil, lactose, maltodextrin, glucose syrup or
starch constituting up to 50% of the end product is added to such plant extracts. As the ratio
of active substances to accompanying plant substances remain unaltered here, the
manufacturer has only to declare the measures he has taken.11
Quality Assurance by Cultivation and Breeding

Although medicinal plant cultivation and breeding are not in the province of pharmaceuticals
technology, but they may have great influence on the use of phyto -pharmaceuticals as useful
medicines.GAP has a major role to play in QA based on the following parameters.
 The fact that that many medicinal substances of natural origin cannot be synthesized
Only with unacceptably great effort, necessitates creation of the natural starting
material i.e., cultivation of the medicinal plant.
60
 The unreliability of supply of drug plants gathered from the wild shows the need for their
cultivation. The qualities available in the often widely scattered gathering areas are
limited. Expert collectors are becoming increasingly difficult to find. All this results in
the increasing occurrence of mistaken identity and adulteration of drug plant materials.
 The increased demands for safety of medicines in general have also led to increasing
demands for the purity and quality of phytopharmaceuticals and of the plant drug
materials from which they are gathered.
 Legal regulations such as the 1973 Washington protection of species agreement and the
more recent 1980West German nature protection order will considerably hinder the trade
and processing of wild plants.11
61
Medicinal plants must be cultivated with phytochemical aspects in view, as the success of
such cultivation depends less on the quality of plants produced and much more on their
quality. The active substance content of a cultivated medicinal plant can be affected by
various factors:
 Genetic variation and hereditary transmission of the secondary substances
 Morpho and ontogenic variability, i.e. differences in the active substances contents in
various parts of the plant and during its growth.
 Environmental influences 21:
- Temperature
- Rainfall
- Day-length and radiation characteristics
- Altitude
- Atmospheric composition
62
SUMMARY
63
. SUMMARY
The present work is an attempt to brief out the various quality assurances of herbal
formulation and their parameters. The quality assurance parameters have been briefly
accounted which are to be strictly followed for the herbal formulations, during and after the
manufacturing process, for the finished products in according to ensure their efficacy,
stability and safety till the shelf life of the products. A description regarding the introduction
and history of herbal formulation usage is presented followed by the difference between
quality assurance and quality control and general concept of quality assurance of herbal
formulations like macroscopic and microscopic characterization. The identification tests for
various herbal substances, herbal preparations and herbal medicinal products are also
described and in brief about physical quality assurance and quality assurance by cultivation
and breeding.
64
CONCLUSION
65
CONCLUSION
Quality assurance of herbal products may be assured by proper control of the herbal
ingredients and by means of GMP. Quality Assurance makes sure you are doing the right
things, the right way. Quality Assurance is a process oriented.. It encompasses the control
and documentation mechanism, which insure, that the multitude of regulations pertaining to
and used in practice of the pharmaceutical industry.
one can not rely upon the quality and efficacy because almost all of the formulations
do not pass through appropriate quality control procedure. The main reason behind
this is the unavailability of systematic quality control procedures for herbal
formulations.
Therefore, the pharmaceutical formulations with combinations of drugs have shown
an increasing trend to counteract other symptoms specific to one drug n formulation, and
hence analytical chemist will have to accept the challenge of developing reliable methods for
analysis of drugs in such formulation.
66
REFRENCES
67
REFRENCES
1) Calixto J.B, “Efficacy, Safety, Quality control, marketing and regulatory guidelines
for herbal medicines; Brazillian Journal of medical and Biological research, Volume
33 (2000), page no.179-189.
2) Edwin E., Sheeza E, Vaibhav J.and Shweta D., “Toxicology of herbs pharma times,
Volume 37, page no. 27-29.
3) Agarwal A., “Critical Issues In quality Control Of Natural Products”, Pharma times,
Volume 37, page no. 9-11.
4) Solescki R.S, A.Neanberthal Flower Berial Of Northern Iraq Science, 4th Edition
1975.
5) Bensky D., Chinese Herbal Materia Madica (Revised edition) 1993.
6) Sarsworth N.R, Higher Plants- The sleeping gained Of Drug Development, American
General of Pharmaceutical Education March, April 46.
7) Ethackerknecht, Therapeutic-From the Primetives to the 20th Century New York

1973.
8) Baby K.L, U Zutschi, C.L Chopra, N.V Amla, “Picrorhiza an Ayurvedic Herb May
Potentiate Photo Chemotherapy in Vitiliva.
9) Journal Of Ethicno Pharmacol 1989.
10) Oxford’s Advanced Learner’s Dictionary”, 7th Edition 729 (2005)
68
11) Dr. Mukherjee k. pulok, “Quality Control Of Herbal Drugs”, first edition 2002,
published by Business Horizons, Page no. 124, 129, 132,186, 189, 193, 214, 217, 219,
653, 658, 679, 680.
12) World Health Organization, “Quality assurance of pharmaceuticals” , 1st edition

reprint 2002 , volume I , published by pharma book syndicate, Hyderabad, page
no.15.
13) World Health Organization, “Quality assurance of pharmaceuticals” , 1st edition

reprint 2002 , volume II , published by pharma book syndicate, Hyderabad
14) Lachman Leon, Lieberman A. Herbert, Kanig L. Joseph, “The theory and Practice of
industrial pharmacy”, 3rd edition , published by Varghese Publishing House, Page no.
297, 298, 299, 300, 301, 302, 303, 804.
15) Kokate C.K., Purohit A.P., Gokhale S.B., 25th edition, December 2003, published by
Nirali prakashan, Pune, Page no. 100, 101, 102, 103, 104.
16) Mosaic, Inc., Software Risk Management Services, 205 N. Michigan Ave., Suite
2211
17) Siverajan V.V and Belachandra I., “Ayurvedic Drugs And Their Plant Sources”,
Oxford And IBH, publishing Co. Pvt. Ltd, New Delhi 50 (1994).
18) Maurice MIWU, Hand Book of African Medicinal Plants, CRC, press Tokyo, 263
(1963).
19) Iyergor M.A. and Nayak S.G.K, Anatomy of Crude Drugs, 8th Edition, 26 (2004).
20) Malik Vijay, “Drugs and Cosmetic Act”, 1940, 7th Edition, published by Eastern
Book company, page no.407.
21) Treas and Evans W.C , “Pharmacognosy”, 14th Edition , published by Harcourt Brace
and Company Asia PTE Ltd , page no. 59,60,61.
69
22) Monomancy T. Labels’ potency claim often inaccurate, analysis finds, Los Angeles
Times 1998 August31;A10
23) Herbal Roulette, consumer Reports 1995;60 (Nov):698-705
24) De Smet PAGM,Toxicological Outlook on the quality assurance of herbal remedies,

Volume I , Berlin:Springer; 1992 , page no. 1-72
25) United States, “USP 25/ Nf20 2002”, First Asian Edition, published by U.S
pharmacopoeia Convention, INC.
26) India, “Indian Pharmacopoeia 1996”, Volume I and II , published by the controller of
publications, Delhi.
27) Eisenberg DM, Davis RB, Ettner SL, et.al Trends in alternative medicine use it the
United States, 1990-1997. JAMA 1998.
28) Brevoort p. The blooming U.S botanical market :a new overview.HerbalGram 1998
Fall;44:33-48
29) John H. Book, Organic Medicinal and Pharmaceutical Chemistry, 11 thEdition, 901
(2004).
30) Chaudhri N.C, Gurbani N.K., “Pharmaceutical Chemistry”, 1st Edition, Vallabh
Prakashan, page no. 187-188(1995).
31) Goyal R.K., “Quality Control of herbal and herbal mineral products”, An emerging
Trend, Pharma Times 37.
32) Harnischfeger G., “Quality Assurance of herbal preparations and herbal medicinal
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1990;5 (suppl 1):126-136
70
Declaration
We hereby declare that the work presented below entitled “Market

Survey Of Antihypertensive Drugs” is full of truth in my knowledge
and belief. We are kinely abide by the rules and regulation of our
institute and university. There is no parallel work is going on this
topic in our institute.
Amit D.Khanvilkar
Aman Preet Duggal
71
72
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Quality Assurance of Herbal Formulations

c100BC First illustrated herbal produced in Greece

c500AD Hippocrates' principles followed in Britain by Myddfai practitioners throughout

Physician Avicenna writes the Canon of Medicine

Various Acts of Parliament passed to introduce some regulation of medical

1800sAD Herbal medicines begin to be eclipsed by mineral-drug based treatments. With

Burgeoning pharmaceuticals industry makes herbal medicine seem outdated.

Post war period sees enormous expansion in the international pharmaceuticals

A handful of dedicated herbalists keep the tradition alive.

A Modern Herbal by Hilda Level is published.

The BHMA produce the British Herbal Pharmacopoeia.

2000AD EU legislation advocates all herbal medicines should be subject to compulsory

UK government currently considering the possible impact and public perception of

In context with pharmaceutical industry quality assurance can be represented as:

Good harvesting practices:

Good manufacturing practices:

Good laboratory practices:

Quality assurance of herbal drugs:-

Quality assurance and quality control confusion

 Quality Assurance: A set of activities designed to ensure that the development

• Odor and Taste :-

• Surface characteristic – Texture and Fracture:-

 Palisade Ratio: It is defined as average number of palisade cells

 Vein – islet number: It is defined as the number of vein –islets per

 Vein- termination number: It is defined as the number of vein let

 Stomatal number: It is average number of stomata per sq.mm of

 Stomatal index: It is the percentage which the number of stomata

Where, S.I. = Stomatal index

S = Number of stomata per unit area

E = Number of epidermal cells in the same unit area 15

These are another important diagnostic characters helpful in the identification of

 Covering trichomes or non-globular trichomes or Clothing trichomes

 Hydathodes or special type of trichomes.15

The primary and most important function of stomata(fig2)is gaseous exchange

 Paracytic or rubiaceos or parallel- celled stomata

 Diacytic or caryophyllaceous or cross-celled stomata

 Anisocytic or cruciferous or unequal-celled stomata

 Anomocytic or ranunculaceous or irregular-celled stomata

 Lycopodium spore method

It is an important analytical technique for powered drugs, especially when

N x W x 94,000x 100 / S x M x P = % Purity of Drug

N = number of characteristic structures (e.g. starch grains)in 26 fields

W =weight in mg of lycopodium taken

S = no. of lycopodium spores in the same 25 fields

M =weight in mg of the sample, calculated on basis of sample dried at 105 °C

P =2, 86,000 incase of ginger starch grains powder

A chromatographic finger print profile represents qualitative/ quantitative determination of

Non-chromatographic Assays (Gravimetric, Titrimetric, and Spectrophotometric) Simpler

• Contaminants, which are impurities such as heavy metals, pesticides, mycotoxins,

• Degradation products, due to the particular nature of herbal medicinal product,

• Residual solvents, which are impurities arising from manufacturing processes.

2) Design and development considerations:

The experience and data accumulated during the development of a herbal

3) Pharmacopoeial tests and acceptance criteria:

The Indian Herbal pharmacopoeia contains important requirements pertaining to certain

Drying and Storage of Plant Drugs

PESTICIDE RESIDUES AND MICROBIAL COUNT

5) Release versus shelf life acceptance criteria: The concept of different

If the herbal substance is not described in the European pharmacopoeia or in another

Leaves, flowers, seeds and fruits - 250 gm

Roots, rhizomes and barks - 500 gm

Cut medicinal plant material - 50 gm

 Acid Insoluble Ash