INTRODUCTION:

The use of herbs as medicine is the oldest form of healthcare known to humanity and has been used in all cultures throughout history. Early humans recognized their dependence on nature for a healthy life and since that time humanity has depended on the diversity of plant resources for food, clothing, shelter, and medicine to cure myriads of ailments. One of the major problems faced by the herbal industry is the unavailability of rigid quality control profiles for herbal materials and their formulations. Primitive people learned by trial and error to distinguish useful plants with beneficial effects from those that were toxic or inactive, and also which combinations or processing methods had to be used to gain consistent and optimal results. Even in ancient cultures, tribal people methodically collected information on herbs and developed well-defined herbal pharmacopeias.^1-2

Standardization of herbal drugs is not an easy task as numerous factors influence the bio efficacy and reproducible therapeutic effect. In order to obtain quality oriented herbal products, care should be taken right from the proper identification of plants, season and area of collection and their extraction and purification process and rationalizing the combination in the case of polyherbal drugs. In India, the department of Ayush, Government of India, launched a central scheme to develop a standard operating procedures for the manufacturing process to develop pharmacopeial standards for ayurvedic preparations.

Medicinal plants are widely distributed throughout the world but most abundantly in tropical countries. It is estimated that about 25% of all modern medicines are directly or indirectly derived from higher plants. Thus, herbal medicine has led to the discovery of a number of new drugs, and non-drug substances. The subject of herbal drug standardizations massively wide and deep. There is so much to know and so many seemingly contradictory theories on the subject of herbal medicines and their relationship with human physiology and mental function. India needs toexplore the medicinally important plants. This can be achieved only if the herbal products are evaluated and analyzed using sophisticated modern techniques of standardization.^3-4

Need of standardization:^5-7

In the global perspective, there is a shift towards the use of medicine of herbal origin, as the dangers and the shortcoming of modern medicine are getting more apparent. It is the cardinal responsibility of the regulatory authorities to ensure that consumers get the medication, which guarantees purity, safety, potency and efficacy. The regulatory authorities rigidly follow various standards of quality prescribed for raw materials and finished products in pharmacopoeias, formularies and manufacturing operation through statutory imposed good manufacturing practices. These procedures logically would apply to all types of medication whether included in modern system of medicine or one of the traditional systems.

It is the cardinal responsibility of the regulatory authorities to ensure that the consumers get the medication, which guaranteed the purity, Safety, potency and efficacy. This duty is discharged by regulatory authorities by rigidity following various standards of quality prescribed for raw materials and finished products in pharmacopoeias controlling manufacturing formula through the use of formularies and manufacturing operation through statutory imposed “Good manufacturing practices”. Herbal products has been enjoying renaissance among the customers throughout the world.

Due to complex nature and inherent variability of the constituents of the plant based drugs, it is difficult to establish quality control parameter and modern analytical technique are expected to help in circumventing this problem. The quality control of crude drugs and herbal formulations is of paramount importance in justifying their acceptability in modern system of medicine. To achieve the desired benefit from herbal preparations, an individual must take the required dose over a certain length of time. Although it is generally believed that most herbal preparations are safe for consumption, some herbs like most biologically active substances could be toxic with undesirable side effects. Therefore, in case of herbal drugs and product, the word “standardization” should encompass entire field of study from cultivation of medicinal plant to its clinical application. Plant material and herbal remedies derived from them represent substantial portion of global market and in this respect internationally recognized guidelines for their quality control are necessary. WHO has emphasized the need to ensure quality control of medicinal plant products by using modern technique and by applying suitable parameters and standards? In order to overcome certain inevitable shortcoming of the Pharmacopoeial monograph other quality control measures must be explored.

Standardization of raw materials includes: -^8-11

Authentication- Each and every step has to be authenticated, area of the collection, parts of the plant collection, the regional situation, as phytomorphology botanical identity, microscopic and histological analysis(characteristic features of cell walls, cell contents, starch grains, calcium oxalate crystals, hairs, fibers, vessels etc.) Several studies of the histological parameters are list of palisade ratio, vein islet number, vein termination, stomatal number, stomatal index, trichomes, stomata, quantitative microscopy, taxonomic identity, foreign matter. Loss on drying, swelling index, foaming index, ash values and extractive values, Chromatographic and spectroscopic evaluation, Determination of heavy metals, pesticide residues, Microbial contamination, Radioactive contamination. The parameter stability of herbal formulations that includes pharmacognostic parameters, physico-chemical parameters, phyto-chemical parameters, microbiological assay, chromatographic analysis.

Pharmacognostic evaluation:

It includes color, odor, taste, texture, size, shape, microscopical characters, and histological parameters.

Physico-chemical parameters:

Each monograph contains detailed botanical, macro-scopic and microscopic descriptions of the physical characteristics of each plant that can be used to ensure both identity and purity. Each description is accompanied by detailed illustrations and photographic images which provide visual documentation of accurately identified material. It includes foreign matter, total ash, acid-insoluble ash, swelling and foaming index, assay, successive extractive values, moisture content, viscosity, PH, Disintegration time, friability, hardness, flow capacity, flocculation, sedimentation, alcohol content.

Chemical parameters:

This covers screening, isolation, identification and purification of the chemical components. Chemical analysis of the drug is done to assess the potency of vegetable material in terms of its active principles. The chemical screening or tests may include colour reaction test, which help to determine the identity of the drug substance and possible adulteration. It includes limit tests, chemical tests etc.

Chromatographic and spectroscopic analysis:

Critical to compliance with any monograph standard is the need for appropriate analytical methods for determining identity, quality, and relative potency. There area plethora of analytical methods available. However, it is often difficult to know which is the most appropriate to use, but critical among know analytical tools in monograph standardization is chromatography.

Full and accurate characterization of plant material requires a thorough physical examination. Microscopic analyses of plants are invaluable for assuring the identity of the material and as an initial screening test for impurities. It includes TLC, HPLC, HPTLC, GC, UV, IR, FT-IR, AAS, LC-MS, GC-MS, fluorimetry etc.

Microbiological parameters:

Pharmacological activity of certain drugs has been applied to evaluate and standardize them. The assays on living animal and on their intact or isolated organs can indicate the strength of the drug or their preparations. These assays are known as Biological assays or Bioassay. It includes the full content of viable, total mould count, total coli forms count. Limiters can be used as a quantitative tool or semi-quantitative to determine and control the amount of impurities, such as reagents used in the extraction of various herbs, impurities ships directly from the manufacturing and solvents etc.

Purity determination:

Each monograph includes standards for purity and other qualitative indices already mentioned above.

Who Guidelines for Herbal formulations:^12-14

The USFDA has issued draft guidance for botanical products. The regulatory approach is based on intended use of botanical – as dietary supplement, cosmetic or drug and status of botanical – marketed in US, marketed outside US or not marketed at all. The guideline is fairly exhaustive and pragmatic. The data requirements depend on several factors.

A. Traditional herbal medicines or currently marketed botanical products, because of their extensive though uncontrolled use in humans, may require less preclinical information to support initial clinical trials than would be expected for synthetic or highly purified drugs.

B. Requirements for Investigational New Drug (IND) applications of botanicals legally marketed in the United States as dietary supplements or cosmetics

C. Requirements for botanical product that has not been previously marketed in the United States or anywhere in the world.

D. Clinical trials of botanical products

E. Documentation for early trials (IND)

F. Exclusive marketing rights

1. Quality control of crude drugs material, plant preparations and finished products.

2. Stability assessment and shelf life.

3. Safety assessment; documentation of safety based on experience or toxicological studies.

4. Assessment of efficacy by ethno medical in formations and biological activity evaluations.

5. 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).

Methods of Standardisation:^15-17

Methodology is divided in to following for the better indulgent:

1. Process standardization

2. Rasausadhis standardization

3. Overview on herbal drug standardization

4. Polyherbal standardization

5. DNA fingerprinting technique

6. Techniques in extraction of herbals

7. Phytosomes/ pharmacosomes: A novel drug delivery system for herbal drugs

8. Instrumental techniques for herbal drug standardization & identification

9. Herbal nanomedicines standardization

10. Global status of the regulatory guidelines for herbal medicines

11. Recent advancement in the methodology for the standardization of herbal medicines.

Critical Factors Affecting the Quality Control of Herbal Drugs:^{18, 19}

1. Microscopic evaluation

2. Foreign matter

3. Ash content

4. Heavy metals

5. Microbial contaminants and aflatoxins

6. Pesticide residues

7. Radioactive contamination

8. Analytical methods

9. Validation

10. Labelling of herbal products

CONCLUSION:

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. Herbal drug standardization is massively wide and deep. Standardization of herbal drugs comprises total information and controls to essentially guarantee consistent composition of all herbals including analytical operations for identification, markers and assay of active principles. Knowledge of Ayurveda is now being imparted through institution, colleges, and hospitals and through ancient treatises. This has necessitated the establishment of standards for ayurvedic drugs and formulations so as to ensure proper use of the medicines so prepared for the benefit of the end user without any unwarranted complications. Now a day’s newer and advanced methods are available for the standardization of herbal drugs like fluorescence quenching, the combination of chromatographic and Spectrophotometric methods, biological assays, use of biomarkers in fingerprinting etc. Bioassay can play an important role in the standardization of herbal drugs and can also become an important quality control method as well as for proper stability testing of the product. Thus standardization is needed to establish quality control parameters for each traditional drug before it is released for use without the fear of toxicity and contamination. There is need for development of techniques which includes both traditional methods of evaluation and modern methods of evaluation. This will improve the quality of the drug and also motivates the practitioners to get more involved in the standardization process. It is recommended that various government agencies should follow a more universal approach to herbal quality by adopting the WHO guidelines and also developing monographs using the various quality parameters outlined above.

REFERENCES:

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17. http://www.reddybams.page.tl/MALLASINDHUR.htm (Accessed 12th April 2012).

18. Krishna gopalshastri, Rasendra sarasangraha, Ajmer: Krishna gopal ayurved bhavan, kaleda. 1/157-158, 2006: 59.

19. Kokate CK and Purohit AP: Nirali Prakashan, text book of pharmacognosy, 34^th edition: 97-132.

Received on 22.03.2016 Modified on 05.04.2016

Res. J. Pharmacognosy and Phytochem. 2016; 8(2): 85-89

DOI: 10.5958/0975-4385.2016.00016.9