In olden times, vaidyas used to treat patients on individual basis, and prepare drug according to the requirement of the patient. But the scenario has changed now; herbal medicines are being manufactured on the large scale in Pharmaceutical units, where manufacturers come across many problems such as availability of good quality raw material, authentication of raw material, availability of standards, proper standardization methodology of single drugs and formulation, quality control parameters.
Ayurveda emphasis the relationship between man and plants throughout the development of human culture. The use of herbal medicine due to toxicity and side effects of allopathic medicines, has led to sudden increase in the number of herbal drug manufactures.1 Herbal medicines as the major remedy in traditional system of medicine have been used in medical practices since antiquity. The practices continue today because of its biomedical benefits as well as place in cultural beliefs in many parts of world and have made a great contribution towards maintaining human health.2
World Health Organization (WHO) has defined herbal medicines as finished labeled medicinal product that contain active ingredients, aerial or underground parts of the plant or other plant material or combinations.3
In almost all the traditional system of medicine, the quality control aspect has been considered from its inspection of itself Rishis, Vaidyas and Hakims. However, in modern concept it require necessary changes in their approach by that way concrete method of quality control in terms development of modern methodologies. Thus today quality assurance is thrust area for the evaluation of traditional used medicinal plants and herbal formulation.
Nature always stands as a golden mark to exemplify the outstanding phenomena of symbiosis. In the western world, as the people are becoming aware of the potency and side effect of synthetic drugs, there is an increasing interest in the natural product remedies with a basic approach towards the nature. Natural products from plant, animal and minerals have been the basis of the treatment of human disease. Today estimate that about 80 % of people in developing countries still relays on traditional medicine based largely on species of plants and animals for their primary health care. Alternative medicine is the needs of the day. Herbal medicines are currently in demand and their popularity is increasing day by day. In the healthcare sector WHO recommends and encourages the use of traditional herbs/remedies because huge amount of raw material is easily available. They are comparatively safe because of their low toxicities. Till today most of the villagers relays on herbal remedies as these have psychological effect on the common man in mind that it will spared of the side effect of allopathic drugs and will magically cured. However, plants are very complex in their composition and their therapeutic activity depends on their chemical constituents, these according to age, geographical location and harvesting processes. Also improper authentication of herbs, adulterations by microorganism, pesticide residue, has made standardization of herbal drug of primary importance.
At present no official standard are available for the herbal preparation. Manufactures those who are doing some testing of their formulation, have fixed their own parameter, most of them are only preliminary in nature. At present it is very difficult to identify the presences of all the ingredients as claimed in a formulation. Hence the first important task is to evolve such parameter by which the presence of the entire ingredient can be identified, various chromatographic and Spectrophotometric methods and evaluation of physicochemical properties can be tried to evolve pattern for identifying the presence of different ingredient. Wherever possible these methods can be applied for quantitative estimation of bioactive group of compounds like alkaloids, flavonoids, polyphenolic components or estimation of particular compound.
In polyherbal Ayurvedic preparations it will be very difficult if we want to estimate each and every ingredient in term of their chemical constituent. But if few major constituents having particular therapeutic action indicated in the labeled can be pinpointed then these constituents should be estimated quantitatively along with the other parameters through which presence of all ingredients can be confirmed. Combined, well coordinated efforts from scientific workers of different disciplines are required for this purpose.
Like any other branch of science and technology, present scenario of herbal medicine has its own limitations arising out of its own technical constituents. The prominent limitations of herbal medicines can be summarized as follow
As may be observed, herbal medicines are not varying effective to treat any acute illness. As most of the medicines are designed to work at molecular level of physiology, the drug takes its time to deliver the results. However there are few herbal medicines which works instantly in acute conditions like diarrhea. On the other hand, modern system of medicine has adequate paraphernalia for management of acute conditions. It has already been established by virtue of its efficacy. It may be a futile exercise to investigate and discover such methods of acute medicinal care within the framework of herbal medicines.
This is the most often criticized aspect of herbal medicines. One important fact is that a herbal medicines. One important fact is that a herbal preparation is administered for its holistic value. Each herbal ingredient in the herbal preparation has an array of chemical constituents with complex molecular formulae. This each herbal preparation is a source of polypharmacy within itself.
As results, standardization of herbal preparation or its ingredients become a highly complex issue. Standardization of herbal drugs by known marker compounds may not be complete answer. Despite it is major limitation, pharmaceutical industry strives hard to have in house specifications based on the quantification of marker compounds. Therefore a consensus is being arrived at to incorporate the qualitative finger-printing together with other physicochemical parameters of quality protocols for herbal medicines is an ongoing process and this shortcoming could be overcome shortly.
Literature on herbal medicines, lack of Lack of scientific data in support of the medicinal activity claimed and their safety and efficacy assumed. Hence there is a need to incorporate certain parameters of the pharmacological evaluation of moderns on modern lines. Who guidelines clearly direct that it is not necessary to carry out detailed toxicological evaluation of herbs and herbal preparation originating from traditional system medicine.
In recent years there is a spurt in the interest regarding survival of Ayurvedic forms of medication. 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 have started getting more apparent, majority of Ayurvedic formulation are prepared from herbs.
It is the cardinal responsibility of the regulatory authorities to ensure that the consumers get the medication, which guarantee. Purity, safety, potency and efficacy. This duty is discharged by the regulatory authorities by rigidity following various standards of quality prescribed for raw materials and finished products in pharmacopoeias controlling manufacturing formulate through the use of formularies and manufacturing operation through statutory imposed “Good manufacturing practices”. All these procedure logically would be apply to all type of medication whether included in modern system of medicine or one of the traditional system such as Ayurvedic system of medicine. Unfortunately the Ayurvedic pharmacopoeias and the formulary have been exempted from the standard attained by present day. Modern medicine, which is continuously undergoing metabolic changes and improvements in the standard of purity, safety and efficacy. Thus maintaining the quality of Ayurvedic medication becomes the sole responsibility of the manufacture.
Herbal product has been enjoying renaissance among the customers throughout the world. However, one of the impediments in the acceptance of the Ayurvedic formulation is the lack of standard quality control profile. The quality of herbal medicine i.e. the profile of the constituents in the final product has implication in efficacy and safety. Due to complex nature and inherent variability of the constituents of 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. But one of the major problems faced by the herbal drug industry is nonavailability of rigid quality control profile for herbal material and their formulations.
Quality controls of synthetic drug offer no problems with very well defined parameters of analysis. In contrast, herbal products represent a number of unique problems when quality aspects are considered. These are because of the nature of the herbal ingredients present therein, which are complex mixtures of different secondary metabolites that can vary considerably depending on environmental and generic factors. Furthermore, the constituents responsible for the claimed therapeutic effects are frequently unknown or only partly explained. These complex positions of quality aspects of herbal drugs are further complicated by the use of combination of herbal ingredients as are being used in traditional practice. It is not uncommon to have as many as five different herbal ingredients in one product. Thus batch to batch variation starts from the collection of raw material itself in the absence of any reference standard for identification. These variations multiply during storage and further processing.
The task of lying down standards for quality control of herbal crude and their formulation involves biological evaluation for a particular disease area, chemical profiling of the material and lying down specification for the finished product. 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 assessment and 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. Quality control has wide connotation and covers; many aspects of drug manufacture, distribution and sale is not restricted to final product analysis either regulatory or otherwise, while engaging in this task, it must be realized that some of the Quality control practices that work excellently either modern drug may not be appropriate with ASU drug.
In India a great deal of bulk knowledge exists among ordinary people about the traditional use of herbal medicine. It is difficult to quantify the market size of the traditional Indian system. Since most practitioners formulate and dispense their own recipes. The present annual turnover of product manufactured by large companies is estimated at approximately US $ 300 million compared to a turnover of approximately US $ 2.5 billions for modern drugs. According to the study on the attitude of modern medicine practitioners are relatively unfamiliar with Ayurvedic product even though some are practiced. They are willing to try an Ayurvedic product if it efficiency is scientifically proven and would try aliment such as cough, cold, diarrhea, stomach problem, reproductive disease, liver and skin disease.4
Patent proprietary Ayurvedic medicines are sold over the counter in pharmacies. These products appear to represent a major share of branded traditional medicine in India. Nevertheless systems like Ayurveda still need to gain an empirical support of modern medical sciences to make them credible and acceptable for all. An innovative research effort to define the advantage of traditional system of medicine with respect to their safety and efficacy could result in a better utilization of these complementary systems of medicine. Internationally several pharmacopoeias have provided monographs stating parameter and standard of many herbs and some product made out of these herbs. Several pharmacopoeias like
Lay down monograph for herbs and herbal products to maintain their quality in their respective nations. Government of India too has brought out Ayurvedic Pharmacopoeia India, which recommends basic quality parameters for eighty common Ayurvedic herbal drugs.
Accounting to WHO it is the process involving the physicochemical evaluation of crude drug covering the aspects, as selection and handling of crude material, safety, efficacy and stability assessment of finished product, documentation of safety and risk based on experience, provision of product information to consumer and product promotion.
Each monograph contains detailed botanical, macroscopic and microscopic descriptions of the physical characteristics of each plant that can be used to insure both identity and purity. Each description is accompanied by detailed illustrations and photographic images which provide visual documentation of accurately identified material.
Full and accurate characterization of plant material requires a combination of physical and chemical tests. Microscopic analyses of plants are invaluable for assuring the identity of the material and as an initial screening test for impurities. Most manufacturers of herbal products lack the quality control personnel to accurately assess plant identity and purity microscopically. The Ayurvedic Herbal Pharmacopoeia (AHP) fully characterize herbal products against the literature and AHP. Verified trade mark authenticated materials to assure identity of test materials. Ideally, submitted materials should be in their whole or semi-whole (cut) form for microscopic assessment. However, much information can be discerned from microscopic evaluation of powders as well.
A chemical method for evaluation covers the isolation, identification and purification. Chemical analysis of the drug is done to assess the potency of vegetable and animal source material in terms of their active principles. The chemical tests include colour reaction test, these tests help to determine the identity of the drug substance and possible adultration.
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. All living organism are used, these assays are known as Biological assays or Bioassay.
Critical to compliance with any monograph standard is the need for appropriate analytical methods for determining identity, quality, and relative potency. There are a plethora of analytical methods available. However, it is often difficult to know which is the most appropriate to use. The primary goal of AHP is to provide multiple methods of identification and testing by which all aspects of the botanical can be appropriately assayed.
Chromatography is the science which is studies the separation of molecules based on differences in their structure and/or composition. In general, chromatography involves moving a preparation of the materials to be separated the "test preparation” over a stationary support. The molecules in the test preparation will have different interactions with the stationary support leading to separation of similar molecules. Test molecules which display tighter interactions with the support will tend to move more slowly through the support than those molecules with weaker interactions. In this way, different types of molecules can be separated from each other as they move over the support material. Chromatographic separations can be carried out using a variety of supports, including immobilized silica on glass plates (thin layer chromatography), very sensitive High Performance Thin Layer Chromatography (HPTLC), volatile gases (gas chromatography), paper (paper chromatography), and liquids which may incorporate hydrophilic, insoluble molecules (liquid chromatography).
Each monograph includes standards of purity and other qualitative assessments which include when appropriate: foreign matter, ash, acid-insoluble ash, moisture content, loss of moisture on drying, and extractives.
High performance thin layer chromatography (HPTLC) is valuable quality assessment tool for the evaluation of botanical materials. It allows for the analysis of a broad number of compounds both efficiently and cost effectively. Additionally, numerous samples can be run in a single analysis thereby dramatically reducing analytical time. With HPTLC, the same analysis can be viewed sing different wavelengths of light thereby providing a more complete profile of the plant than is typically observed with more specific types of analyses.
When applicable, the most appropriate quantitative analytical method with accompanying chromatograms shall be provided. The primary goal of the method(s) is to provide validated methods to be used for the quantization of the compound(s) most correlated with pharmacological activity or qualitative markers as determined by the primary pharmacological literature, constituent declaration in product labeling, and a survey of experts. The method(s) will be selected from the primary analytical literature by a Methods Selection Committee with priority given to compendial methods when available. In this context, validation consists minimally of a two-lab validation using the same procedures, samples, and reference standards.
Primary factors for considering a method as appropriate include accuracy of the findings, speed, basic ruggedness, applicability to a large segment of the manufacturing community, and avoidance of the use of toxic reagents and solvents. In an attempt to promote harmonization, primary consideration is given to those methods which are already accepted in official pharmacopoeias or by AOAC International. When necessary, comparative tests shall be conducted to determine which of the available method(s) is most appropriate. The validation process minimally includes: standard precision, linearity, sample precision using replicate samples, sample linearity, selectivity (co-elution, sensitivity to analyte degradation), retention times, and limits of detection. Other methods which may be of value to the industry may be included or cited in the monograph but are not required for compliance with the monograph.
Manish S. Wani
Working as Lecturer at MAEER’s Maharashtra Institute of Pharmacy, MIT campus, Pune. He has done his M.Pharm in Pharmaceutics from Pune University. He has also done his MBA from Pune University
Prof.(Dr). S. R. Parakh
Working as Principal and Professor in Pharmaceutics at MAEER’s, Maharastra Institute of Pharmacy, MIT Campus, Pune-411038
Dr. M.H. Dehghan
Working as Principal and Professor in Pharmaceutics at Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad-431001
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Prof. Satish A. Polshettiwar
Working as Lecturer at MAEER’s, Maharashtra Institute of Pharmacy, MIT Campus, Pune. He has done his M.Pharm in Quality Assurance from Nagpur University. He is a Life member of APTI. He has published and presented several research articles in national level and International level
E.Mail: firstname.lastname@example.org, Cell No. 09422842838
Prof . V.V.Chopade
Working as Lecturer at Siddhant college of Pharmacy, Sadumbare, Pune. He has done his M.Pharm in Quality Assurance from NagpurUniversity
Mr. S. B. Chepurwar
Working as Research Associate at Emcure Pharmaceuticals Limited, Pune. He has done his M.Pharm in Pharmaceutical Chemistry from North Maharashtra University, Jalgaon. E-mail: email@example.com