THE USE OF QUALITY CONTROL PARAMETERS IN THE EVALUATION OF VEGETABLE CRUDE DRUGS

THE USE OF QUALITY CONTROL PARAMETERS IN THE EVALUATION OF VEGETABLE CRUDE DRUGS

CHAPITRE ONE

INTRODUCTION

THE STUDY’S HISTORY

Plants’ universal involvement in disease therapy is shown by their use in all major medical systems, regardless of the underlying philosophical foundation. In many situations, how and when such medicinal plants were initially employed is lost in prehistory; moreover, animals other than humans appear to have their own materia medica (Prajapati et al., 2003). Nonetheless, it is certain that the vegetable kingdom existed prior to the arrival of man on Earth. As man became more acquainted with his surroundings, he became more knowledgeable about plants, as these were the only therapeutic agents he possessed. He was able to sort out which plants could be eaten as he matured and evolved, but he also began to correlate healing properties with particular plants.

According to the World Health Organization (WHO), 4 billion people (80% of the world population) already use herbal medicine for some type of primary health care. Early humans recognized their reliance on nature for a healthy life, and humanity has relied on the diversity of plant resources for food, clothing, shelter, and medicines to cure a wide range of maladies ever since. Man, on the other hand, did not need modern methods of study to gather a materia medica of plants, which he frequently employed in connection with magical and other ritual rituals. It is intriguing to consider that such a collection of herbal medicines created over centuries by trial and error, presumably with the patient as the experimental animal throughout, must surely contain some components worthy of future examination and should not be dismissed too easily.

Medicinal plants are extremely valuable in the treatment and cure of sickness. Scientific study has enhanced our understanding of the chemical actions and composition of the active elements that determine the therapeutic capabilities of plants over time. It is now widely known that plant treatments and therapies are far safer than manufactured pharmaceuticals for treating complex ailments. Many alkaloids, glycosides, and antibiotics have been isolated, identified, and used as cures. As people become more aware of the strength and side effects of synthetic pharmaceuticals, there is a growing interest in plant-based therapies with a basic approach to nature in the Western world. The future development of Pharmacognosy and the herbal medication industry will be heavily reliant on accurate approaches for identifying marker chemicals in extracts, as well as standardization and quality control of these extracts.

Little more needs to be said about the current importance of medicinal plants because it is obvious that the plant itself, whether in the form of crude drugs or, more importantly, medicinally active materials isolated from them, has been and will continue to be an important aid to physicians in the treatment of disease.

1.2 NATURAL MEDICINE

An herb is a plant or component of a plant that is prized for its medicinal, fragrant, or savory properties. Herbs can be thought of as biosynthetic chemical laboratories that produce a variety of chemical substances. Herbal treatments or medications are made up of plant parts or unpurified plant extracts that contain numerous ingredients that often operate synergistically. Herbal medicines are classified into three types, according to the WHO: raw plant material, processed plant material, and therapeutic herbal products. Herbal medications are labeled finished goods that contain active substances such as aerial or underground plant parts or other plant material or a mix thereof, whether in their raw form or as plant preparations. Herbal medicine, often known as herbalism, is the therapeutic or medicinal use of herbs or herbal products. They can be made from any part of the plant, but the most common are leaves, roots, bark, seeds, and flowers. They are consumed via eating, drinking, inhaling, or applying topically to the skin. Herbal products frequently contain a variety of naturally occurring plant biochemicals, many of which contribute to the medical advantages of the plant. Chemicals recognized to have therapeutic advantages are referred to as “active ingredients” or “active principles,” and their existence is dependent on a variety of circumstances such as plant species, harvest time and season, soil type, and how the herb is processed. In addition to the active ingredients, herbal medicines may contain excipients.

Herbal medications are those that comprise plant material mixed with chemically defined active compounds, including chemically defined, isolated elements of plants. In some cultures, herbal remedies may, by tradition, contain natural organic or inorganic active components that are not of plant origin.” Copper and colleagues (1986).

Herbal medication use has skyrocketed, mirroring a global trend of individuals reverting to natural therapies. Herbal medicine products, which are available as tablets, capsules, powders, teas, extracts, and fresh or dried plants, are nutritional supplements that people take to improve their health. Herbs have long been seen to be safe, and they are increasingly being used by people who do not have a prescription. However, some can be harmful to one’s health, while others are ineffective and may interact with other medications. To minimize confusion with culinary herbs, herbs and plant extracts with therapeutic properties are referred to as “Herbal Medicinal Products.”

Historically, religious practice and the use of magical ceremonies had a large influence on sickness cure and the usage of medicinal herbs. The study of herbal medicines differs little from that of allopathic medicinal plants in terms of pharmacognosy. In actuality, many herbal treatments have not been as well examined, either pharmacologically or phytochemically, a situation that must alter as tougher licensing regulations are established for over-the-counter items.

Natural remedies have gained popularity and acceptability in both developing and developed countries over the last decade. Because of poverty and limited access to modern medicine, over 80% of the world’s population, particularly in developing countries, uses herbal medicine as their major source of healthcare (Bodeker et al., 2005; Mukherjee, 2002; Farnsworth et al., 1985; Bisset, 1994). Traditional medical practice is frequently regarded as an intrinsic element of these societies’ culture. People in the West are drawn to herbal remedies for a variety of reasons, the most important of which is that, like our forefathers, it is believed they will help us live healthier lives. Herbal remedies are frequently regarded as a more balanced and mild approach to treatment. Individuals that utilize herbal items as home treatments and over-the-counter medications spend billions of dollars on them. As a result, they account for a sizable share of the worldwide drug market (WHO, 2005, 2002a; Blumenthal et al., 1998; Roberts and Tyler, 1997; Farnsworth et al., 1985).

Herbal Medicinal Products (HMPs) make up the majority of what is sometimes referred to as Complementary and Alternative Medicine (CAM), and are at one end of a spectrum that ranges from “healthy foods” to “nutraceuticals” to “herbal medicinal products,” which are products primarily used in the treatment or prevention of disease. However, it should not be forgotten that these advances in medicine and therapy are easily accessible to only a small percentage of the world’s population. For economic or geographical reasons, herbal products are the primary, if not the only, source of medication in many regions, primarily in developing countries, but also in pockets throughout every affluent society. In contrast, they are utilized as a matter of choice rather than need in more affluent parts of the world. Several serious reasons have been advanced for the renewed interest in the use of HMPs. This includes a reaction to the serious side-effects that can occur when using orthodox drugs, particularly the more potent ones; the inability of western medicines to treat some diseases satisfactorily, particularly chronic conditions; and the widely held misconception that “natural” must be better or safer.

To obtain the desired benefit from herbal remedies, an individual must consume the prescribed dose over a specific time period. Although most herbal preparations are generally thought to be safe for consumption, some herbs, like most biologically active substances, may be toxic with undesirable side effects (Bisset, 1994).

Herbal medicine is typically aimed at restoring homeostasis, or a natural physiological balance of the body, rather than immediately targeting disease symptoms. The plant extracts given will contain a diverse spectrum of plant metabolites, some of which will be therapeutically active. This combination, which contains a variety of plant cell elements, may have less negative effects than a single isolated principle. A variety of elements that may appear pharmacologically inactive on their own combine synergistically to provide therapeutic effects.

Herbal products are typically introduced into the market in most countries without sufficient scientific review or any required safety and toxicological investigations. There is no efficient machinery in place to oversee manufacturing procedures and quality requirements. Consumers can purchase herbal products without a prescription and may be unaware of the possible dangers of a subpar product. One of the most critical conditions for the development of a quality drug is a well-defined and consistent drug composition. Given the nature of plant-derived goods, which are not normally constant and are dependent on and impacted by a variety of circumstances, assuring continuous product quality is critical for the industry’s survival and success (Bauer, 1998).

The concentration of active principles in herbal formulations must be standardised in order to determine the quality of medications. A vital requirement of industry and other organizations dealing with ayurveda and herbal products is quality evaluation of herbal preparation. The expanding public usage of botanicals (plant-derived drugs and other goods) is driving efforts to evaluate the health claims of these agents and set quality and manufacturing standards. It is obvious that the herbal sector must adhere to tight norms, and such laws are required.

1.3 BOTANICAL HERB STANDARDIZATION AND QUALITY OF BOTANICAL PREPARATIONS:

Plants have hundreds of elements, some of which are present in very low amounts. Despite the availability of advanced chemical analytical technologies, phytochemical research rarely succeed in isolating and characterizing all secondary metabolites contained in the plant extract. Aside from that, plant constituents vary greatly depending on a variety of factors, making quality control of phytotherapeutic agents difficult. 2004 (Jablonski). There are various procedures involved in quality control and standardization of herbal medicines. The source and quality of raw materials, on the other hand, are critical in ensuring the quality and stability of herbal remedies. Other factors, such as the use of fresh plants, temperature, light exposure, water availability, nutrients, period and time of collection, method of collection, drying, packing, storage, and transportation of raw material, age and part of the plant collected, and so on, can all have a significant impact on the quality and thus therapeutic value of herbal medicines. Because some plant constituents are heat labile, plants containing them must be dried at low temperatures. Enzymatic reactions that continue for lengthy periods of time after plant collection also degrade other active principles. This explains why the content of herbal-based medications is frequently highly diverse. As previously stated, aside from these variable aspects, additional factors such as extraction method and contamination with microbes, heavy metals, pesticides, and so on can also interfere with the quality, safety, and efficacy of herbal pharmaceuticals. For these reasons, pharmaceutical corporations prefer cultured plants over wild-harvested plants since their contents vary less. Furthermore, and perhaps more importantly, when medicinal plants are grown, the main secondary metabolites can be monitored, allowing the best harvesting period to be determined. (2004) (Koo et al.).

Quality control of herbal medicines is an important problem to consider when ensuring therapeutic efficacy, safety, and rationalizing the use of herbal medicinal products (HMPs) in healthcare. Prior to determining the relevance of current efficacy and safety data, the material must be defined and characterized. It is also critical that the material used and commercially available be consistent with the evaluated material, because any significant change in quality would need a re-evaluation of the relevance of the safety and efficacy results (Mukherjee, 2002). Adulterants, and more often than not, inaccurate herb identification, are the root reasons of poor herbal quality.

Standardization is a system that assures that each dose contains a predetermined amount of quantity, quality, and therapeutic impact of substances. Herbal products cannot be considered scientifically legitimate unless the medicine tested has been authenticated and described to assure reproducibility in product manufacturing. Furthermore, many dangerous and lethal side effects, such as direct toxic effects, allergic reactions, contaminant effects, and interactions with herbal drugs, have recently been reported. The phytochemical ingredients of a herbal preparation determine its therapeutic activity. Scientists face a significant problem in developing authentic analytical methods that can reliably profile the phytochemical composition, including quantitative studies of marker/bioactive chemicals and other important ingredients. Standardization is a key step in establishing a standard biological activity, a consistent chemical profile, or simply a quality assurance program for herbal medication manufacture and manufacturing. Authenticating herbal medications and distinguishing adulterants from genuine medicinal herbs are critical for both pharmaceutical companies and public health, as well as ensuring reproducible quality of herbal medicine. (2011) (Choudhary and Sekhon).

It is critical to establish a standardized system for all plant medicines on the market since the potential for variance in different batches of medicine is significant. Plant materials’ therapeutic effects may differ depending on where they are collected, when they are collected, whether they are collected at the same time and place but in different years, and the environmental factors surrounding the cultivation of a particular medicinal plant. This variation is exacerbated by the fact that in herbal therapy, several plants may be utilized in the same formulation. This indicates that a quality control test for the complete preparation should be performed to assure the preparation’s quality (Prajapati et al., 2003).

1.4 TRADITIONAL METHOD FOR STANDARDIZING HERBAL FORMULATIONS

Standardization of herbal raw pharmaceuticals includes raw plant drug passport data, botanical authentication, microscopic and molecular investigation, chemical composition identification using various chromatographic techniques, and biological activity of the entire plant. Various workers have reported macroscopic and microscopic evaluation and chemical profiling of herbal materials for quality control and standardization. Macroscopic identification of medicinal plant materials is based on sensory evaluation factors such as shape, size, color, texture, odor, and taste, whereas microscopy entails a comparative microscopic analysis of powdered herbal medication. Furthermore, the use of light and scanning electron microscopes (SEM) in herbal drug standardization has increased the accuracy and capabilities of microscopy as a means of herbal crude material identification. Furthermore, chromatographic, spectrophotometric, and combination of these methods, electrophoresis, polarography, and the use of molecular biomarkers in fingerprints are currently used in the standardization of herbal drugs (Choudhary and Sekhon, 2011).

1.5 CURRENT REGULATIONS FOR CRUDE DRUGS STANDARDIZATION

Several pharmacopoeias around the world have issued monographs outlining the parameters and standards for many herbs and the products made from these herbs. Several pharmacopoeias, for example:

Pharmacopoeia Commission

Herbal Pharmacopoeia of China

The Herbal Pharmacopoeia of the United States

Herbal Pharmacopoeia of the United Kingdom

Herbal Compendium of the United Kingdom

Japanese Herbal Medicine Standards

India’s Ayurvedic Pharmacopoeia

Establish a monograph for herbs and herbal products in order to keep their quality in their different countries (Agarwal, 2005).

1.6 STANDARDIZATION AND QUALITY CONTROL PARAMETERS FOR HERBAL CRUDE DRUGS EVALUATION

Standardization and quality control of herbals, according to WHO (1996a and b), is the process involved in the physicochemical evaluation of crude drug covering aspects such as crude material selection and handling, finished product safety, efficacy, and stability assessment, documentation of safety and risk based on experience, provision of product information to consumers, and product promotion. Normally, attention is drawn to quality indices such as:

In the case of complete pharmaceuticals, the macroscopic and secondary characteristics are sufficient for identifying the correct variety and searching for adulterants.

Microscopic examination is useful for both powders and ungrounded medications to identify the correct type and search for adulterants.

Foreign organic materials: To obtain the medication in its purest form, matter other than the parent plant must be removed.

Total ash, sulphated ash, water soluble ash, acid insoluble ash, and other ash values are used to determine the identity and purity of crude drugs.

Moisture content: Testing for moisture content aids in reducing inaccuracies in estimating the real weight of drug material. Low moisture indicates better product stability against degradation.

Extractive values are the approximate weights of the extractable chemical elements of crude drug in various solvent environments.

Crude fiber: This is a criterion for measuring cleanliness and aids in determining the woody material component.

Qualitative chemical evaluation entails identifying and characterizing crude drugs in terms of phytochemical constituents. It uses several analytical techniques to discover and isolate active components. Botanical identification, extraction with appropriate solvents, purification, and characterisation of active components of medicinal value are all part of phytochemical screening approaches.

Chromatographic investigation includes rudimentary drug identification using key chemical ingredients as markers.

Quantitative chemical evaluation: estimating the amount of the major constituent classes.

Solubility: Solubility, particularly extraordinary solvent behavior, is useful in the study of numerous oils and oleo-resins.

Physical Constituents: Specific gravity, optical rotation, viscosity, and refractive index are particularly useful for evaluating fats, oleo-resins, balsams, and related substances.

Swelling Index: This index assesses the swelling capacity of medicinal plants.

Volatile Oils: It refers to the measuring of the plant’s volatile content.

Bitterness Value: The bitter characteristics of plant materials are measured by comparing the threshold bitter concentration of the materials’ extract to that of a dilute solubility of guanine hydrochloride.

Hemolytic Activity: The hemolytic activity of a plant material or a saponin-containing product is measured by comparing it to the activity of a reference material, saponin.

The foaming ability of an aqueous decoction of plant materials and extracts is assessed using a foaming index.

Pesticide Residue: It quantifies pesticide residues in plants.

Contamination of medicinal plant materials with arsenic and heavy metals can be attributable to a variety of factors, including environmental contamination and pesticide residues.

Microorganisms: Current harvesting, processing, and production procedures may result in increased pollution and microbial proliferation.

Aflatoxins: Because their existence in crude drugs can be hazardous, their presence is being investigated.

DNA Fingerprinting: This technique is beneficial for distinguishing genuine medications from substituted or counterfeit drugs that are phytochemically indistinguishable.

Chemical fingerprinting: To detect all of the components in the extracts.

Biological profiling: This technique identifies physiologically active plants, allowing for very comprehensive standardization and quality control.

Radioactive Contamination: Exposure to ionizing radiation cannot be avoided because there are several sources, including radionuclides found naturally in the ground and atmosphere.

Toxicological tests: To aid in the determination of pesticide residue and potentially hazardous materials, safety tests in animals such as LD50 and microbial count approaches are used to determine their presence or absence.

1.7 DETERMINATION OF PURITY

Purity is directly related to drug safety and deals with aspects such as ash values, contaminants (for example, foreign matter in the form of other herbs), and heavy metals. Modern purity evaluation, however, covers microbiological contamination, aflatoxins, radioactivity, and pesticide residues due to the use of enhanced analytical technologies. Photometric analysis, thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and gas chromatography (GC) can all be used to determine the consistent content of herbal remedies (Kunle et al., 2012).

High Performance thin layer chromatography (HPTLC) is an important quality assessment method for botanical materials. It enables the efficient and cost-effective examination of a wide range of chemicals. The same analysis using HPTLC can be studied using several wavelengths of light, offering a more complete profile of the plant than is generally visible with more particular types of studies (Chakravarth, 1993).

1.8 WORLD HOSPITAL ORGANIZATION GUIDELINES FOR QUALITY STANDARDIZED HERBAL FORMULATIONS

WHO has developed guidelines to assist member nations in developing national policy on traditional medicine and researching its potential utility, including evaluation, safety, and efficacy. The following core factors serve as standardization and quality control parameters for herbal formulations:

Control of the quality of raw pharmaceuticals, plant preparations, and finished goods.

Shelf life and stability evaluation.

Safety evaluation; safety documentation based on experience or toxicological investigations.

Ethno medical information and biological activity evaluations are used to assess efficacy.

1.9 CRUDE MATERIAL QUALITY CONTROL

Quality is described as a drug’s status as determined by its identity, purity, content, and other chemical, physical, or biological attributes, as well as the manufacturing procedures. Quality control refers to the processes that are engaged in ensuring the quality and validity of a manufactured product.

The efficacy and safety of herbal medicine are affected by the quality of the ingredients in the final product. With very well specified parameters of analysis, quality controls of synthetic drugs pose no challenges. When it comes to quality, herbal goods, on the other hand, present a number of distinct challenges. This is due to the nature of the herbal components, which are complex combinations of several secondary metabolites that can change significantly depending on environmental and general conditions. Furthermore, the constituents allegedly responsible for the therapeutic effects are frequently unknown or only partially explained. These nuanced viewpoints on quality characteristics of herbal medications are exacerbated further by the usage of herbal ingredient combinations as employed in traditional practice. It is fairly uncommon for a product to have up to five different botanical constituents. In the absence of a reference standard for identification, batch to batch variance begins with the acquisition of raw materials. These differences compound during storage and subsequent processing.

The task of establishing quality control standards for herbal crude and their formulation entails biological evaluation for a specific disease area, chemical profiling of the material, and establishing specifications for the finished product. As a result, in the case of herbal treatments and products, the term “Standardization” should embrace the full field of study, from medicinal plant cultivation through clinical application (Wani, 2007).

To assure the safety and quality of medicinal plants, researchers must concentrate on all elements of medicinal plant research, including ethno-pharmacology, use, isolation and identification of active ingredients, efficacy evaluation, safety, formulation, and clinical evaluation. The quality monitoring of medicinal plants begins at the source of the plant material. The phytochemical composition of plant material and the resulting quality can vary due to a variety of factors, including geographical location, soil quality, temperature, and rainfall, among others. Taxonomy, time of collection, method of collection, cultivation, harvesting, drying and storage conditions, preparation and processing methods can also affect composition. Contamination by bacteria, chemical agents such as pesticides and heavy metals, as well as insects and animals during any of these stages can also result in poor product quality. Standardization of all of these parameters is required to achieve current quality, safety, and efficacy criteria (Brijesh et al., 2006).