Bottle Necks in Standardization of Traditional System of Medicines
K. Jayaram Kumar
In general, however, increased use of TM/CAM has not been accompanied by an increase in the quantity, quality and accessibility of clinical evidence to support TM/CAM claims.
Herbal products are the most commonly used complementary and alternative therapies.
The medical and research community is constantly searching for new natural agents.
Natural products are now a multibillion-dollar industry in the developed countries
and these products are used by millions of people annually. Consumers now regularly
ask most pharmacists about the benefits of natural products in treating their
medical conditions. Consumers are bombarded with recommendations from friends,
family, television advertisements and magazine articles giving advice about
natural remedies. Herbal products are widely perceived as being safe by patients
because they are considered natural. Most medications before being offered to
consumers undergo rigorous evidence-based clinical testing; this is not necessarily
true for herbs. Consumers regularly use these products without the knowledge
of their healthcare professionals (Eisenberg et al.,
1993, 1998). Therefore, it is important for developing
better standardization techniques for traditional medicines. Plant species contain
bewildering diversity of secondary metabolites. Accuracy in recording or observing
the medicinal use of a plant, determining whether the ethno medical use can
be demonstrated under scientific conditions in laboratory and/or chemical characterization
of compounds and role of placebo effect are important issues that need to be
verified in the development of drugs of plant (Kumar et
al., 2004, 2005).
STANDARDIZATION OF HERBAL MEDICINE OF TRADITIONAL SYSTEM OF MEDICINE
Herbal medicine has its basis in the traditional system of medicine like Ayurveda,
Unani, Kampo, Malay Chinese system of medicine etc. These traditional systems
of medicine have been used for centuries and have certain standard procedures
for its preparation and standardization. The cultural aspects of herbalism in
different countries and societies play an important role to see the diversity
of worldwide herbal use. In the traditional system of medicine like Ayurveda
drugs are classified based on the Panca mahabhuta (Earth, water, fire, space
and ether) is explained in association with its rasa (taste), guna (properties)
and karma (action). The potency of the drug (veerya), target site (substratum),
time of action (kala), stratagem (upaaya), targeted delivery with specific intention
(abhipretha) are also expressed in the natural language which is associated
with human cognitive processes, such as thinking and reasoning. Similarly all
other traditional system of medicines has their own method of standardization
for assuring quality most in human linguistic terms. This method of evaluation
has to be taken into consideration in standardization of herbal medicine (Kumar
et al., 2004, 2005; Venugopal,
WHO Guidelines for Quality Standardized Herbal Formulations (WHO,
control of crude drugs material, plant preparations and finished products
assessment and shelf life
assessment; documentation of safety based on experience or toxicological
of efficacy by ethnomedical informations and biological activity evaluations
The bioactive extract should be standardized on the basis of active principles
or major compounds along with the chromatographic fingerprints (TLC, HPTLC,
HPLC and GC). The standardization of crude drug materials includes the following
(Stage of collection, parts of the plant collected, regional status, botanical
identity like phytomorphology, microscopical and histological analysis,
taxonomical identity, etc.)
matter (herbs collected should be free from soil, insect parts or animal
evaluation (sensory characters taste, appearance, odor, feel of
the drug, etc.)
||Tissues of diagnostic importance present in the drug powder
values and extractive values
and spectroscopic evaluation. TLC, HPTLC, HPLC methods will provide qualitative
and semi quantitative information about the main active constituents present
in the crude drug as chemical markers in the TLC fingerprint evaluation
of herbals (FEH). The quality of the drug can also be assessed on the
basis of the chromatographic fingerprint
of heavy metals-e.g., cadmium, lead, arsenic, etc.
residue-WHO and FAO (Food and Agricultural Organization) set limits of
pesticides, which are usually present in the herbs. These pesticides are
mixed with the herbs during the time of cultivation. Mainly pesticides
like DDT, BHC, toxaphene, aldrin cause serious side-effects in human beings
if the crude drugs are mixed with these agents
contamination-usually medicinal plants containing bacteria and molds are
coming from soil and atmosphere. Analysis of the limits of E. coli
and molds clearly throws light towards the harvesting and production practices.
The substance known as afflatoxins will produce serious side-effects if
consumed along with the crude drugs (Table 1).
contamination-Microbial growth in herbals are usually avoided by irradiation.
This process may sterilize the plant material but the radioactivity hazard
should be taken into account. The radioactivity of the plant samples should
be checked accordingly to the guidelines of International Atomic Energy
(IAE) in Vienna and that of WHO
for microbial contamination
should be completely removed or should not be present
In order to obtain quality oriented herbal products care should be taken right
from the proper identification of plants; season and area of collection, extraction,
isolation and verification process. Chemical and instrumental analyses are routinely
used for analyzing synthetic drugs to confirm its authenticity. In the case
of herbal drugs, however the scene is different especially for polyherbal formulation,
as there are no chemical or analytical methods available. Therefore, biological-screening
methods can be adopted for routine checkup of herbal drugs and formulations.
In the case of herbal drugs, the quality of raw materials and products can be
furnished by regular pharmacognostic identifications and phytochemical analysis.
The herbal formulations in general can be standardized schematically as to formulate
the medicament using raw materials collected from different localities and a
comparative chemical efficacy of different batches of formulation are to be
observed. The preparations with better clinical efficacy are to be selected.
After all the routine physical, chemical and pharmacological parameters are
to be checked for all the batches to select the final finished product and to
validate the whole manufacturing process.
The stability parameters for the herbal formulations which includes physical parameters, chemical parameters and microbiological parameters.
Physical parameters include color, appearance, odor, clarity, viscosity, moisture content, pH, disintegration time, friability, hardness, flowability, flocculation, sedimentation, settling rate and ash values.
Chemical parameters includes limit tests, extractive values, chemical assays, etc.
Chromatographic analysis of herbals can be done using TLC, HPLC, HPTLC and GC, UV, Fluorimetry, GC-MS, etc.
Microbiological parameters include total viable content, total mold count, total enterobacterial and their count. Limiters can be utilized as a quantitative or semiquantitative tool to ascertain and control the amount of impurities like the reagents used during abstraction of various herbs, impurities coming directly from the manufacturing vessels, impurities from the solvents, etc.
Chemical decomposition of substances present in the formulation also produces several toxic or impure compounds during storage in undesirable conditions. Contaminants may come directly from the atmosphere also. This include mainly dust, sulfur dioxide, H2S, CO2, arsenic, moisture, etc.
The guidelines set by WHO (Shrikumar et al., 2004)
can be summarized as follows:
to the identity of the drug. Botanical evaluation sensory characters,
foreign organic matter, microscopical, histological, histochemical evaluation,
quantitative measurements, etc.
to the physiochemical character of the drug. Chromatographic profiles,
ash values, extractive values, refractive index, polarimetric readings,
moisture content, volatile oil content, etc.
to the pharmacological parameters. Biological activity profiles, bitterness
values, haemolytic index, astringency, swelling factor, foaming index,
details heavy metals like cadmium, lead, arsenic, mercury, etc.,
contamination- Total viable aerobic count, pathogenic bacteria like enterobacteria,
E. coli, salmonella, Pseudomonous aeruginosa, Staphylococcus
aureus, etc. and presence of afflatoxins etc.
Modern herbal ayurvedic monographs: In the modern herbal ayurvedic monographs the standardization parameters are discussed in a comprehensive way. According to the modern ayurvedic monograph the quality control protocols include the following:
Title, synonyms, publications related to that plant, constituents present, analytical methods.
Descriptive evaluation: Description of the drug, phytomorphological, microscopical, organoleptic evaluations, foreign matter, foreign minerals, etc.
Physicochemical parameters: Identity: Physical and chemical identity, chromatographic finger prints, ash values, extractive values, moisture content.
Strength: Ethanol and water extractive values, volatile oil and alkaloidal assays, quantitative estimation protocols, etc.
Biological activity evaluation: Bitterness values, astringency, swelling factor, form index, hemolytic index, etc.
Toxicological evaluation: Pesticide residues, heavy metals, microbial contamination like total viable aerobic count, pathogens like E. coli, Salmonella, P. aeruginosa, S. aureus, Enterobacteria, etc.
Aflatoxins: The presence of aflatoxins can be determined by chromatographic methods using standard aflatoxins B1, B2, G1, G2 mixtures. Aflatoxin is a product of the microbial strain Aspergillus flavus.
Bottle backs of the existing methods are:
evaluation: One cannot identify the adulterant in powdered drug. e.g.,
Flower bud of clove is substituted by mother clove and clove stalk which
contains starch and sclereids, which is absent in bud, respectively
content: It is not practicable method if drug contains other volatile
substances like essential oil, ethers, esters etc.
solid: Total solid content remain in range even after addition of impurity
content: Tannin content of a drug can be maintained in range by adding
adulterated or substandard drug
selected marker compound does not represent the wholesome nature of the
abundance of a particular compound depends on several factors ranging
from seasonal to regional collection and ways of harvesting
formulations can always be spiked with markers thereby enhancing the chances
concept of holistic approach of Ayurveda is not really met with these
In modern method of analysis many sophisticated instruments like HPLC, HPTLC,
U.V are used along with the characterization of compounds isolated. Now a days
importance is given on chemical constituents and negation of human cognitive
processes such as thinking and reasoning which forms the core of traditional
medicine. Does this justify the time tested traditional medicine? Imposition
of standardization techniques using modern analytical methods will risk of loosing
time tested medicine. With the world turning towards herbal medicine it is time
to develop methods to standardize the traditional medicine with methods incorporating
traditional and modern analytical method. Many small industries involved in
preparation of herbal medicine are closing. The objective of United Nations
Industrial Development Organization (UNIDO) for systematic utilization of the
renewable natural resource for the benefit of the populace and increasing the
industrial output will have serious set back. We will be risking the popular
medicine in which most of people place faith with lack of proper standardization
methods. There is need for development of techniques which includes both traditional
methods of evaluation and modern methods of evaluation of traditional medicine.
The coupling techniques like fuzzy logic, neural networks and accurate linguistic
models along with modern analytic methods of analysis (Kumar
and Bhatnagar, 2006). This will improve the quality of the drug and also
motivates the traditional medicine practitioners to get more involved in the
standardization process." class="btn btn-success" target="_blank">View Fulltext