WHO Guidelines For Herbal Drug Standardization
Sapna Shrikumar*, M. Uma Maheswari, A. Suganthi, T.K. Ravi.
Department of Pharmaceutical Analysis, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore-44, India.
The growth of pharmaceutical industry is based on continuing success in producing new products whether they are used as therapeutic or prophylactic agents. The role of R&D is pivotal in this endeavor.
Pharmaceutical research is aimed at meeting the medical needs of the population for whom appropriate therapeutic remedies are not available or at those that are available are unsafe for prophylactic use for various disorders. While meeting medical needs, research also has to ensure that market needs for such exist and that the product will command sales and profits proportionate to investments. In cases where there are mismatches between these two, the products suffer the status of orphan drugs. The selection of an appropriate R&D portfolio is a strategic management exercise for a company, which should take into account apart from medical needs, innovative potential for success and available resources.
WHO Guidelines for Quality Standardized Herbal Formulations
a.Quality control of crude drugs material, plant preparations and finished products.
b.Stability assessment and shelf life.
c.Safety assessment; documentation of safety based on experience or toxicological studies.
d. Assessment 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 include the following steps:
1.Authentication (Stage of collection, parts of the plant collected, regional status, botanical identity like phytomorphology, microscopical and histological analysis, taxonomical identity, etc.)
2.Foreign matter (herbs collected should be free from soil, insect parts or animal excreta, etc.)
3.Organoleptic evaluation (sensory characters – taste, appearance, odor, feel of the drug, etc.)
4.Tissues of diagnostic importance present in the drug powder.
5. Ash values and extractive values.
7.Moisture content determination
8.Chromatographic 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.
9.Determination of heavy metals – e.g. cadmium, lead, arsenic, etc.
10.Pesticide 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.
11.Microbial 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.
Limits for Microbial Contamination
Total aerobic bacteria
Afflatoxins should be completely removed or should not be present.
12.Radioactive 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.
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 is 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 preparation 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 can be summarized as follows:
a.Reference to the identity of the drug. Botanical evaluation – sensory characters, foreign organic matter, microscopical, histological, histochemical evaluation, quantitative measurements, etc.
b.Reference to the physiochemical character of the drug. Chromatographic profiles, ash values, extractive values, refractive index, polarimetric readings, moisture content, volatile oil content, etc.
c.Reference to the pharmacological parameters. Biological activity profiles, bitterness values, haemolytic index, astringency, swelling factor, foaming index, etc.
d.Toxicity details – heavy metals like cadmium, lead, arsenic, mercury, etc. Pesticide residues.
Maximum residue limits =
Acceptable daily index x body weight x extraction factor
--------------------------------------------------------------- x Therapeutic doses
Mean daily intake of drug x safety factor x 100
e.Microbial contamination – Total viable aerobic count, pathogenic bacteria like enterobacteria, E. coli, salmonella, Pseudomonous aeruginosa, Staphylococcus aureus, etc. and presence of afflatoxins etc.
f. Radioactive contamination.
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.
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.
Pesticide residues, heavy metals, microbial contamination like total viable aerobic count, pathogens like E. coli, Salmonella, P. aeruginosa, S. aureus, Enterobacteria, etc.
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.
Classical Evaluation as per Ayurvedic Literatures
Classical therapeutical attributes like Rasna, Guna, Virya, Vipaka and Karma classical formulations, doses, storage conditions.
The quality of the raw materials can be tested according to the following format:
Name of the drug (English, Regional names, Exact botanical nomenclature)
Part of the plant used
Area of collection
Season of Crop
Time and year of collection
Pesticide and insecticides
Condition of the drug (fresh or dry)
Form of the drug (powdered or intact or cuttings like etc.)
The subject of herbal drug standardization is massively wide and deep. There is so much to know and so much seemingly contradictory theories on the subject of herbal medicines and its relationship with human physiology and mental function.
For the purpose of research work on standardization of herbal formulations and neutraceuticals a profound knowledge of the important herbs found in India and widely used in Ayurvedic formulation is of utmost importance.
India can emerge as the major country and play the lead role in production of standardized, therapeutically effective ayurvedic formulation. India needs to explore the medicinally important plants. This can be achieved only if the herbal products are evaluated and analyzed using sophisticated modern techniques of standardization such as UV-visible, TLC, HPLC, HPTLC, GC-MS, spectrofluorimetric and other methods.