HARAR HEALTH SCIENSE COLLEGE DEPARTMENT OF PHARMACY Course Title: Pharmacognosy |. Introduction to Pharmacognosy For Second Year BSc. Pharmacy (B. Pharm.) Student By:-Introduction to Pharmacognosy eContent e Definition, Historical developments and scope of Pharmacognosy Relation of pharmacognosy with other pharmacy disciplines e Crude drugs:- Source of drugs, Classification of drugs e Study of Medicinal Plantse Objectives At the end of the chapter the student should able to: +* Explain the definition , history and Scope of Pharmacognosy * Describe classification and source of drug * To study on medicinal plant List factor affecting The Quality of Active ingredient +* Explain different drug quality evaluation techniqueIntroduction Definition e The term pharmacognosy was first coined by Johann Adam Schmidt (1759-1809) e The term pharmacognosy is derived from two Greek words V pharmakon = drugs V gignosco = to acquire a knowledge of drugsDefinition, History and Scope of Pharmacognosy Classically pharmacognosy was defined as the knowledge (study) of drugs Vv Pharmacognosy studies natural substances used in the treatment and prevention of diseases or having biologically activities on living organismsCont... e The scientific and systematic study of the structural, physical, chemical, biological and sensory characters of crude drugs of vegetable, animal and mineral origin including their: Vv history, V cultivation of the medicinal plants v methods involved for their collection Vv preparation for the commerce and Vv other particulars related to the treatment they received during their passage from the producer to the distributor or pharmacist.History of Pharmacognosy e The earliest archeological finding is the pollen grains of eight spices at a burial site of Neanderthal man (around 60,000 B.C) in Shanidar (Iraq) e Yarrow (Achillea) ..... antispasmodic e Marshmallow (A/thaea) ..... as laxative e Groundsel (Senecio) ...... emmenagogue e Centaury (Centaurea) ...... for indigestion e Ephedra (Ephedra) ..... for asthma e Muscari (Muscari) ..... for skin disorderse Ancient Egyptian papyruses contained a number of herbs many of which have survived through ages (speculated to come from around 3000 BC). e The healing of sick is carried out by the priest doctor and his son pharmacist for prescription and preparing of drug. e The second oldest surviving recorded information on medicinal plants is that of the Babylonian; Law code of Hammurabi (1700 BC). e most of their drug are obtained from vegetables.e The Chinese has also contributed a lot to the development of pharmacognosy @ In 1578 AD, A book entitled Pen T’sao Kan Mu (Herbal with commentary) was published. e The book contained 1892 drugs e Hippokrates (460-375 BC) utilized many simple natural remedies.— Theophrathus (340 BC) wrote De Historia Plantarum and De Causis Plantarum. e These books described many medicinal plants, how they are used in medicine, how to grow them and many other related observations. e Krateus (100 BC) wrote the first illustrated book on medicinal plants. e The book has not survived but is believed to have influenced later works.e Dioscorides Pedanius of Ananzarbos (75 BC) wrote De Materia Medica, 80 % of which consists of herbs. e The book was used as authoritative sources of drug information until the Renaissance. e The book described more than 500 plants, individually in the following layout: Vv plant name, synonyms and picture Vv habitatsVv Botanical description v Drug properties or action V Medicinal usage Vv Harmful side effects V Quantities and dosage Vv Harvesting, preparation and storage instructions Vv Adulteration and method of detection Vv Veterinary usee Claudius Galen was physician to five Roman emperors. e He was a teacher, philosopher, pharmacist and leading scientist of his day. e During his life he produced five hundred books and treatises on all aspects of medical science and philosophical subjects and e his ideas were to formulate many of the scientific beliefs which dominated medical thinking for about 1500 years.e Galen was the great compiler and systemizer of Greco-Roman medicine, physiology, pharmacy and anatomy. e Galen's influence can be still seen today. e The word “galenic" is used to describe drugs and medicines made from vegetable and animal ingredients using prescribed methods. The Persian, Ibn Sina (AD 980-1037) also called Avicenna by the western world, composed the Kitab ash-shifa (Book of Healing) and Canon of Medicine.e Spanish Muslims contributed tremendously to the development of descriptive botany of medicinal plants. E.g Al-Ghafiqi (died in 1165) e William Withering (1785) discovered the use of digitalis and published "An Account of the Foxglove and Some of its Medicinal Uses". e Friedrich Wilhelm Adam Serttirner (1803) discovered morphine and recognized then the new class of natural substances, alkaloids.e Pierre-Joseph Pelletier and Joseph-Bieniamin Caventou isolated v Emetine from ipeca-cuanha (1817) Vv Strychnine and brucine from nux-vomica (1818) Vv Quinine and cinchonine from cinchona bark (1820)Scope of Pharmacognosy %* Pharmacognosy is not only important as academic exercise. % It is the infra- structure on which evaluation of novel medicines depends ¥V Identifying biological sources of drugs Vv Assessing the efficacy and safety of herbal drugs or their constituents as therapeutic agents using scientific methodsVCultivation of medicinal plants Visolation and Analysis of phytochemical VPreparations of general tonics and stimulants Vin steroid industry, Tissue culture VHerbal and antibiotics preparations v Securing regular supply of natural products by: e Cultivation e increasing yield oozing For 2 year Se Pharmacy (B Pharm) students BY:- Menbere D.Cont... V Incorporation of a natural product in the system of modern medicine v Pharmacognosy is an applied science, which deals with the botanical, biochemical and economical features of natural remedies.v¥Pharmacognosy is a broad discipline, which has adopted different concepts from various disciplines like chemistry, pharmacology, botany, agronomy, biotechnology, biochemistry and medicine. VMost of the pharmacognostic studies are generally focused on medicinal plants/ herbal medicines.Why do we study pharmacognosy? Vv Herbs and natural products offer a very good alternative source of drugs * The share of natural products in modern medicine is as high as 45 % in developed countries x In developing countries about 80 % of the population, rely on natural remedies and almost every individual is believed to use herbal drugs at least occasionally.% Plants are considered as big laboratories and mankind is said to have used less than 3-5 % of what nature can potentially provide. % Natural products are more tolerated by the body Vv The study natural products can generate valuable information for the synthetic chemistCrude drugs e Crude drugs are vegetable or animal drugs that have undergone no other processes than collection and drying, but they may be powdered. elt means the harvested and usually dried plant or animal sources of pharmaceutically or medicinally useful products before they have undergone extensive processing or modification.Source of drug There are two origins(sources) for each drug; the natural or biological, as well as, the geographical origin. The natural or biological origin (source( The natural origin of a drug is the plant or animal yielding it, if a plant, botanical origin or botanical source and if an animal, zoological origin or source.Geographical sources of drugs * The geographical source or Habitat is the region in which the plant or animal yielding the drug grows. vPlants growing in their native countries are said to be indigenous to these regions e.g. Hyoscyamus muticus of Egypt, ‘annabis sativa of India. vPlants are said to be naturalized when they grow in a foreign land or in locality other an their native home.e Drug obtained from different source include : Mineral source: liquid paraffinJMgSo4 Animal: insulin, thyroid extract, Heparin Plant: Morphine, digoxin, atropine, castor oil Synthetic source: Sulphonamide , Aspirin, AZT Microorganism: Antibiotics Genetic Engineering: Human insulin, human growth hormone + + + + HOFClassification of drug e Vegetable drugs can be arranged for study under the following headings. 1. Alphabetical: Either Latin or vernacular names may be used. e This Arrangement is employed for dictionaries , pharmacopoeias etc. e Although suitable for quick reference it gives no indication of interrelationships between drugs.2. Taxonomical: on the basis of an accepted system of botanical classification the drugs are arranged according to the plants from which they are obtained, in classes, orders, families, genera and species. 3- Morphological: dividing the drugs into groups e.g. leaves, flowers, fruits, seeds,..... which are referred to as "organized drugs", and e groups as dried lattices, extracts, gums, resins, oils, fats and waxes which are known as “unorganized drugs".Cont... 4- Chemical: the drugs are divided into groups according to their most important constituents e.g. drugs containing volatile oils, glycosides, alkaloids, bitter principles, tannins, saponins........ 5- Pharmacological and therapeutic effects: %* Grouping of drugs according to the pharmacological action of their most important constituents or their therapeutic use. e.g. astringent, irritant, drugs affecting the gastrointestinal tract, drugs promoting systemic effects on the muscle and nervous system, drugs affecting the circulatory system, drugs used chemotherapeutically for the treatment of infectious diseases, etc....Study of Medicinal plant e Botanical Nomenclature (The binomial system) * Is due to Swedish biologist Linnaus, % inthis system the first letter of the first name, which is always spelt with Capital letter, denotes the genus. * whilst the second name denotes the species * The first letter of species names written with small initial letter e.g. Strychnos potatorum .eThe specific name is usually chosen to indicate: 1- Some striking characteristics of the plant: a- Hyoscyamus muticus (muticus = short). The plant being short. b- Aaane belladonna (bella = beautiful, donna =la y, the juice of the berry placed in the eyes causes dilatation of the pupils, thus giving a striking appearance).cont... 2- A characteristic colour: a- Piper nigrum (= black) b- Citrus aurantium (= golden yellow) c- Digitalis purpurea (= purple) 3- An aromatic plant or certain aroma: a- Myritaceae fragrans (having a fragrant, nice aroma) b- Caryophyllus aromaticus (refers to the aroma)Cont... 4- A geographical source or history of a drug: a- Cannabis indica (growing in India) b- Tamarinds indica (India) 5- A Pharmaceutical activity or an active constituents: a- Papaver somniferum (sleep inducing) b- [pomoea purga (laxative). 6- A general meaning or a special indication a- Allium sativum (= cultivated) b- Triticum vulgaire (= wild)Types of preparations from plants * Fresh plant * Crude drugs e Crude drugs are the correct part(s) of medicinal plants that have passed through the processes of collection and drying. e Possibly they may be grinded or shredded.* Cont... Vv Crude extracts (extractives) Vv Crude drugs may be boiled with water or oil. Vv Crude drugs may be extracted with other appropriate solvents. Vv Simple formulations (usually liquid) could also be prepared from crude extracts. * Fractions V Solvent fractions could be prepared from crude extracts based solubility E.g.: methanol fraction, acetone fraction, butanol fraction etc. Vv Fractions could also be prepared on the basis of class of natural products. E.g.: flavonoidal fraction, alkaloidal fraction, saponin fraction etc.* Cont... * Isolated pure compound e Single pure compounds that are responsible for the medicinal properties of a plant could also be isolated and then formulated in conventional dosage forms. E.g.:- Reserpine is isolated from Raulfia serpentinaand formulated as tablets for hypertension e Ephedrine is isolated from Ephedra spp. and formulated as tablets, injection or powder for injection for asthma and chronic bronchitise Note: The decision at which stage to make the drug available to consumers depends on: e@ SAFETY FACTORS * Generally safety increases as we go from fresh plant material to isolation of pure compounds e EFFICACY FACTORS :Generally efficacy increases as we go from fresh plant material to isolation of pure compounds * in many cases however, isolated compounds may not be as effective as extractives because of perhaps additive or synergistic effectsV Quality:Quality increases as we go from fresh plant material to isolation of pure compounds V Economical factors :Production cost increases as we go from fresh plant material to isolation of pure compounds e To determine at which stage to use a medicinal plant as therapeutic agent, thorough study must be conducted on its constituents e In order to study plant constituents they must be extracted from the plant first.Examples of Crude Drugs e Crude drugs e It means the harvested and usually dried plant or animal sources of pharmaceutically or medicinally useful products before they have undergone extensive processing or modification. e Examples of Crude Drugs e Entire plants or animals: Mentha, Lobelia, Cantharidis, Cochineal.Examples of Crude Drugs Entire organs of plants or animals: Senna, Clove, Fennel, Linseed, Quassia, Cinchona, Liquorice, Thyroid gland. e Minerals: chalk, kaolin, talc. e Substances derived from plants or animals (unorganized): opium, aloes, tragacanth, resins, musk, beeswax, gelatin.e Crude drugs of natural origin can be categorized:- + Organized (cellular) drugs and % Unorganized (acellular) drugs e Organized drugs e comprise those crude drug materials which represent part of the plant/animal and are therefore made up of cells for e.g. Digitalis leaves, Cinchona bark, Sandalwood, Rauwolfia roots, Nux-vomica seed, etc.e Unorganized drugs edo not have morphological or anatomical organization. %* These include plant exudates such as: Vv v aad gums (e.g. Acacia, Tragacanth); oleagum resin (myrrh), plant latex like opium, euphorbia latex and extracts of seeds (fixed oils e.g. Arachis oil).* Cellular drug Acellular * ‘ve defined cellular Don't ‘ve well defined structure structure * They are direct part of Plant or animal product obtained plant or animal through incision, extraction * Solid in nature Solid, semisolid and can be liquid * Identified by Identified through their morphologic organoleptic properties Eg. Digitalis leaves, cinchona gums bark, Rauwolfia root Vv extracts of seeds (fixed oils e.g. Arachis oil).Plant metabolite e All plant can produce chemical compound as part of their metabolic activity. primary metabolite- found in all C plant = eg. Sugar & fat phytochemical Cc Secondary metabolite- in some plant * Secondary metabolite: it's metabolite and pigment have therapeutic value and refined to produce drug. eg. Quinine from cinchona , digoxin from fox gloveEND THANK YOUHARAR HEALTH SCIENSE COLLEGE DEPARTMENT OF PHARMACY Course Title: Pharmacognosy ll. Factors Affecting the Quality and/or Quantity of Active Ingredients For 2" Year BSc. Pharmacy (B. Pharm.) Student By:-Factors Affecting the Quality and/or Quantity of Active Ingredients 4.1 Chemical races e 4.2 Geographical variations e 4.3 Season and time of collection e4.4 Drying 4.5 OthersFactors Affecting the Quality and/or Quantity of Active Ingredients e Objectives At the end of the chapter the student should able to: * List factor affecting The Quality of Active ingredient * Explain different drug quality evaluation techniqueFactors Affecting the Quality and/or Quantity of Active Ingredients e Introduction e QUALITY:- is the status of a drug that is determined by identity, purity, content, and other chemical, physical, or biological properties, or by the manufacturing processes. e Quality control is a term that refers to processes involved in maintaining the quality and validity of a manufactured producte In general, quality control is based on THREE IMPORTANT PHARMACOPOEIAL DEFINITIONS: 1. Identity: ls the herb the one it should be? v Can be achieved by macro- and microscopically. 2. Purity: Are there contaminants/adulterants e.g., in the form of other herbs which should not be there?* The analytical methods can be employed in order to establish the constant composition of herbal preparations e Photometric analysis, @ Thin layer chromatography (TLC), e High performance liquid chromatography (HPLC), a e Gas chromatography (GC)3. : Is the content of active constituents within the defined limits? The most difficult one to assess, since in most herbal drugs the active constituents are unknown. Sometimes markers can be used which are, by definition, chemically defined constituents that are of interest for control purposes, independent of whether they have any therapeutic activity or not.e Where no active constituent or marker can be defined for the herbal drug, the percentage extractable matter with a solvent may be used as a form of assay, an approach often seen in pharmacopeias._Factors affecting crude drug quality e The term quality when applied to crude drugs covers a number of aspects including: Vv Correct identity Vv Absence of adulterants Vv Absence of contaminants V Suitable levels of active principlese To identify the various factors that can affect the quality of crude drugs it is useful to examine the way in which crude drugs are obtained and eventually reach the ultimate user |. Plant growth e Medicinal plants may either be cultivated on farms or may be collected from wild sourcese Cultivation may enable to control many variables that affect quality; however, it is not always the ultimate solution. e Factors affecting the amount and nature of active constituents during plant growth are: V Genetics V Growth conditions e Climate Soil Altitude e Rainfall Temperature Day lengtha) Genetics/ chemical races Genetic variants of the same species may yield different levels of the same active constituents/ different type of active constituents/both “chemical races” have been identified in many medicinal plants including: Papaver purpurea, Withania sominifera, Digitalis lanata Pharmaceutical importance of the knowledge of chemical races V_ To select high quality chemical strains V To eliminate chemical strains with toxic effectsCont....... b) Growth conditions:- can affect not only the health growth of the plant but also the content of active constituents. * Climate:- include: temperature, rainfall, hours of daylight, etc. V Plants grown in different climatic conditions will be of different quality, and even those grown in the same area will vary in quality from year to year due to climatic conditions For example: V Aloes need heavy rain fall to produce good yield of anthracene glycosides.Temperature * Major factor controlling the development and metabolism of plants * Higher temp. favors the formation of volatile oil * The mean optimum temperature for nicotine production from Nicotina rustica is 20°c. % Fixed oil produced at low temp contains fatty acids with a higher content of double bond * Cannabis grown in tropical climates has higher yield of the THC (tetrahydrocannabinol) than grown in temperate areasRainfall e Annual rain fall, its distribution through out the year, its effect on humidity, and its effects water holding capacity of soil has effects on vegetation e Continuous rain fall can lead to a loss of water soluble substances from leaves and root parts by leaching Glycosides Alkaloids Volatile oilsDay length e A factor which determine the amount of glycosides and alkaloids produced by plants e In stramonium, belladona & cinchona — full sunshine gives higher contents of alkaloids e In Datura stramonium varieties long exposure to bright light brought about a sharp increase in the hyoscine content at the time of flowering e Marigold flower- more carotinoids with longer day light but with more radiation oxidized to carotin ion.Altitude * Athigh altitude tea plants grow well (1000-2000) coca plants (100-200) coffee plants (800-1800) V The bitter constituents of plants like Gentiana lutea increase with altitude V Quantity of alkaloids of aconitum & lobelia in flora decrease with altitude v Thyme and peppirmint yield less volatile oil at higher altitude Vv Pyrethrum gives more pyrethrines at higher altitudesSoil: soil pH, texture & mineral content will affect plant growth e All plants require Ca for their normal nutrition but plants like Pinus pinaster & D.purpureacan not grow on chalky soil e Generally nitrogen fertilizers increase the size of plants & amounts of alkaloids producedB. Collection e Drug may be collected from either cultivated or wild plants. e Those drugs obtained from cultivated are more reliable than wild plant. * The amount of a constituent is not uniform throughout life of plant. %* The stage at which a plant is collected or harvested is therefore important for maximizing the yield of the desired constituentCont... * Plants may be collected by semi-skilled or unskilled labor %* The quality of crude drugs may be affected due a number of factors during collections: a) Correct identification of the plant * The plant may accidentally or deliberately replaced or contaminated with a different species.b) Time of collection( season) %* The amount as well as the nature of active constituents of plants may show seasonal and diurnal variations Rhubarb @ Winter...... Anthranols = Summer... Antraquinones Colchicum = Autumn... Starch, no colchicine (devoid of bitterness) = Spring...... Bitter intaste due to colchicine Hyoscaymus_ # Wintev...... Less alkaloid m= Summer... High % of alkaloide Time of the day e Plants constituent may vary in amount according to the time of the day Diaitalis * Afternoo * Hiah% of cardiac Ralanaceo * Afternoo * Low %.efalkaloid usleaves Ni... % Low%of >> but x Morning * high of adkateidesCont... * Stage of maturity and age The value and content of active constituents of many drugs depends on the stage of maturity and age. — Example:- clove flower bud contain volatile oil but as the flower starts to mature, less volatile oil and more starch is produced — Conium fruits contain coniine when fruits are mature and unripe. — Santonica flowers are rich in santonin when unexpanded, when it starts to open, the santonin content decreases when it become expanded.Cont... e To ensure maximum quality crude should be collected at: I. The appropriate season II. Particular stage of development III. Particular age e Place to be avoided for collection of medicinal plant: * Road side , mining sites %* Drainage ditches, * Around industries facilityCont... c. Rules for collection e the material is best collected when the organ in question has reached its optimal state of development: 1. Roots are collected in spring, before the vegetation process stops. 2. Rhizomes collected when they store ample of reserve food materials and maximum chemical constituents 3. Bark is collected in the spring & early summer.4, Leaves are collected before they reach their flowering stage; e.g. senna, digitalis, belladonna etc., while leaves of aloe are collected when they are sufficiently thick 5. Flowers are usually gathered before pollination or many times before their full expansion (in dry weather during morning hours. 6. Fruits are collected while ripe or half ripe.Cont... 7. Resins, gums,lattices- are collected as soon as they ooze out of the plants Acacia gum- collected 2-3 weeks after making incisions on the tree & is sufficiently hard Opium & papaya lattices- collected after coagulation of lattices Balsam of peru & terpentine oleo resin are collected when the plants are about 8-10 years oldC) Method of collection:- Plants can be collected manually or by mechanical collectors %* Mode of harvesting varies with: Vv The drug being produced Vv The pharmaceutical requirement i. Hand labor * Merit: Skilful selection of plant parts * Demerit : Time consuming , Cost ii. Mechanical devices * Merit : Highspeed ,Less cost * Demerit : Plant parts not skilfully collectedDrying of crude drugs Reasons for drying: 1. 2. 3. To help in their preservation. To fix their constituents, by preventing reactions that may occur in presence of water. To prevent the growth of micro-organisms such as bacteria and fungi. . To facilitate their grinding. . To reduce their size and weight. . Insufficient drying favors spoilage by micro- organisms and makes it possible for enzymatic destruction (>10%)Fast drying (excess heat) may lead to decomposition of active constituents Sunlight may result in photo degradation The air temperature is kept at 20-40 °C for thin materials such as leaves, but is often raised to 60-70 °C for plant parts that are harder to dry, e.g. roots and barks. Depending upon the type of chemical constituents, a method of drying can be two types:1- Natural drying: this is accomplished by direct sun- drying or shade. 2- Artificial drying: this is a rapid method done at well-controlled temperature @ It accomplished through: e Direct fire, use of heated stones, use of stone elyphophilaization (freeze drying)- for heat sensitive substance like antibiotics and proteins . e Chemical drying * Absolute dried drug is that completely freed from water.Stabilization * On long storage, enzymatic reactions will slowly destroy the constituents, because the last traces of water can never be removed. %* In order to avoid this degradation, the enzymes should be destroyed before drying, a process usually called stabilization. % ~The most common method being brief exposure (a few minutes only) of the plant material to ethanol vapor under pressure (0.5 atm).e Stabilization may be of value for the isolation of compounds that are very susceptible to enzymatic degradation.3. Storage of crude drugs * There are great differences in the stability of crude drugs because of slow enzymatic changes in the constituents. * Drugs containing glycosides and esters are usually less stable than those containing alkaloids. * Drugs with essential oils deteriorate rather quickly through evaporation, oxidation and polymerization of the substances constituting the essential oil,eTannins on the other hand, have an almost unlimited durability %* Drugs usually deteriorate along the time of storage, except in few cases e.g. Cascara should not be used except after certain period of storage. %* Improper methods of storing and inadequate protection during storage can cause a pronounced deterioration.Cort... In order to keep crude drugs as long as possible: * Itis essential to store them in a dry condition in carefully closed containers * Itis also advisable to exclude light * Itis also necessary to protect the drug against insect attack.Grinding of crude drugs % Regardless of whether the crude drug is to be used for isolation of a pure compound or for manufacture of a simple preparation, the first operation that must be performed is grinding of the plant material to a powder of suitable particle size. * Itis important that the particles are of as uniform size as possible. * Excessive dust can clog percolators and result in a turbid extract which is hard to clarify.Cont.... Large particles take a longer time for complete extraction than small ones. * Large differences in particle size thus slow down the extraction process. Grinding produces a certain amount of heat which must be observed when grinding crude drugs containing heat-sensitive compounds. Cold grinding is also preferable for crude drugs containing volatile oils. Following grinding, the material must be sifted to ensure the proper particle size.%* Common machine used for grinding of crude drug include: I.Hammer mill- most commonly used II. Knife mill- useful for production of low dust powders of leaves, barks and roots for subsequent percolation or maceration III. Tooth mill- used for production of very fine powderAdulteration of Herbal Drugs % Adulteration is the introduction of organic or inorganic material (other than that specified in the official descriptions of the drug) by human factors * Adulteration may be as accidental or deliberate * Adulteration may occur as:- Vv Admixture:- mixing of the drug with other material or V Substitution:- complete substitution of the drug by another substanceCont... e Types of adulteration and means of detecting them a) Accidental adulteration * Occurs as a part of the normal process of collection of the drug and its preparation for the market * Accidental adulteration may be tolerated as long as it is with the specified pharmacopoeial limit (e.g. in BP usually 2% w/w)It may comprise:- i. Presence of inorganic matter e.g. soil, sand * Detected by high ash values, macroscopic and microscopic examination ii. Presence of parts of the plant other than the official part * These other organs may contain a low amount of active constituents or none at all or may contain toxic compounds * Detected by macro/micro examinationsCont... iii. Presence of other plants growing on or together with the drug plant and collected in the harvesting process * Detected by macro/micro examinations, chromatographic profile iv. The wrong plant collected by mistake instead of the genuine one by unskilled collectors * Detected by macro/micro examinations, chromatographic analysis, chemical testsb) Deliberate adulteration * Deliberate adulteration usually takes place when the drug in question is expensive/high price and/or there is shortage of supply %* Admixture or substitution is carried out to sell the poorer quality drug at the regular price * The adulterant is a readily available cheaper, often worthless materiale Common types of adulterants employed for deliberate adulteration: a) Completely different plant with superficial resemblance to the authentic drug = Detected by macroscopical/microscopical examinations, and chemical tests b) A species closely related to the official drug but with slightly different constituents or lower amounts of the active compounds = Detected by careful macro/micro examinations, chromatographic profile, assay proceduresc) The same species as the official drug but an inferior commercial variety with lower active compounds or slightly different constituents = Detected by chromatographic profile, assay procedures d) The authentic species from which the active compounds have been extracted (exhausted material) = Detected by assay procedures e) Simulated worthless structures made to look like the authentic drug = Detected by macro/micro examinatione When the plant material is powdered, adulteration is more difficult to detect by macroscopical/morphological examination eCommon adulterants of powders are sawdust, ground nutshells, starch, chalk, sand and other mineralsDeterioration e Deterioration is a decline in quality of a drug due to the influence of other living organisms or physicochemical factors e When insects or larger animals are involved, the drug is said to be infested e Deterioration of a drug may take place at any point after its collection e It occurs specially during:- e During storage period e During packaging and transportation, etce The shelf-life of crude drugs are influenced by many factors which include not only the quality of storage conditions but also the stability of the secondary (2°) metabolites present therein. e There are two principal reasons for deterioration: a) Physicochemical factors e.g. light, heat, oxygen, water which promote chemical reactions either directly or by activation of enzymes b) Biological factors:- microbial contaminations, insects and rodentsPhysicochemical factors 1. Moisture: moisture sometimes affects drugs adversely through activating the enzymes (as in cardiac glycosides). 2. Heat: rise of temperature up to 45°C activates the enzymes causing decomposition of active constituents. Volatile oil containing drugs are also affected by higher temperatures, their content decreases.3. Air: oxygen of air oxidizes certain. constituents of crude drugs, eg. linseed and lemon oil, it causes rancidity of fixed oils 4. Light: it affects drugs, especially those having marked colours. ee. diellow colour of Rhubarb changes to reddish tint, ewhite coloured corollas turn brown.Biological factors 1. Bacteria: cotton fibres are rendered brittle by bacterial attack which makes the cotton wool objectionable and dusty. 2. Moulds: the mycelium of delicate hyphae produces an unpleasant mass of clinging particles in powdered drugs. 3. Insects: they seem to attack all drugs but have preferences to certain drugs as ginger, elladonna, kola, liquorice... e Insects which infest vegetable drugs include beetles, mites and moths. They render drugs porous and powdery.Methods for controlling insects 1. Heat treatment: it is the simplest method and is done by exposing the drug to a temperature of 60-65. e lt is effective especially for insect eggs which are not affected by insecticides. 2. Fumigation: this is done by volatile insecticidal agents in closed areas e.g. CS2, CN. e Most fumigants do not kill eggs of insects. elt is advisable to repeat fumigation at intervals to obtain better results.3. Low temperature storage: this method is preferred to fumigants. Adult insects, pupae, larvae and eggs are sometimes killed by very low temperatures. 4. Exposure to alternate periods of low and high temperatures: frequently is more effective for killing insects than a prolonged period of low temperature exposure. Rodents: they cause much spoilage of crude drugs during storage, especially if wrapped in paper, cloth or put in cardboard or wooden containers. The presence of rodent's filth, excreta, hairs causes rejection of the drug.Method of evaluations 1) Macroscopic Evaluation e This evaluation procedure provides the simplest and quickest means to establish the identity and purity and thereby ensure quality of a particular sample. e If it is found to be devoid of or significantly different from the specified sensory characters like colour, consistency, odour, etc., it is considered as not fulfilling the requirements.Cont.... e However judgment based on the sensory characteristics like odour, taste etc., may vary from person to person and time to time based on individual's nature e No preliminary treatment is necessary for evaluating the sample in this manner excepting the softening and stretching of the wrinkled and contracted leaves and flowers etc.2. Microscopic Evaluation e Microscopic evaluation :done in laboratory by the use of microscope and utilize various characters of drug for evaluation such as types and arrangement of various cells and tissues. e It is indispensable in the initial identification of herbs, as well as in identifying small fragments of crude or powdered herbs, and detection of foreign matter and adulterants.e Microscopic analysis is needed to determine the correct species and/or the correct part of the species present. e For instance, e pollen morphology may be used in the case of flowers to identify the species, and the presence of certain microscopic structures such as leaf stomata can be used to identify the plant part used. — Itis of prime importance, especially when different parts of the same plant are to be used for different treatments.3. Determination of Foreign Matter e Herbal drugs should be made from the stated part of the plant and be devoid of other parts of the same plant or other plants. e They should be entirely free from moulds or insects, including excreta and visible contaminant such as sand and stones, poisonous and harmful foreign matter and chemical residues.e “Invisible” microbial contaminants, which can produce toxins, are also among the potential contaminants of herbal medicines. e Macroscopic examination can easily be employed to determine the presence of foreign matter, although microscopy is indispensable in certain special cases (e.g., starch deliberately added to “dilute” the plant material). e when foreign matter consists, e.g., of a chemical residue, TLC is often needed to detect the contaminants.4. Determination of Ash %* To determine ash content the plant material is burnt and the residual ash is measured as total and acid-insoluble ash. * Total ash is the measure of the total amount of material left after burning and includes ash derived from the part of the plant itself and acid- insoluble ash.% Acid-insoluble ash is the residue obtained after boiling the total ash with dilute hydrochloric acid, and burning the remaining insoluble matter. Vv This procedure measures the amount of silica present, especially in the form of sand and siliceous earth.5. Determination of Heavy Metals %* Contamination by toxic metals can either be accidental or intentional. %* Contamination by heavy metals such as Hg, Pb, Cu, Cd, and As in herbal remedies can pose Clinically relevant dangers for the health of the user* Asimple, straightforward determination of heavy metals can be found in many pharmacopeias and is based on color reactions with special reagents such as thioacetamide or diethyldithiocarbamate, and the amount present is estimated by comparison with a standard.* Instrumental analyses have to be employed when the metals are present in trace quantities, in admixture, or when the analyses have to be quantitative. e.g., Atomic absorption spectrophotometry (AAS), neutron activation analysis (NAA).6. Determination of Microbial Contaminants and Aflatoxins %* Medicinal plants may be associated with a broad variety of microbial contaminants such as bacteria, fungi, and viruses. * Inevitably, this microbiological background depends on several environmental factors and exerts an important impact on the overall quality of herbal products and preparations.%* Herbal drugs normally carry a number of bacteria and molds, often originating in the soil. * Poor methods of harvesting, cleaning, drying, handling, and storage may also cause additional contamination For 2nd Year BSc. Pharmacy (B. os Pharm) Student By:- Menbere D. 7Cont... * In general, a complete procedure consists of determining the total aerobic microbial count, the total fungal count, and the total Enterobacteriaceae count, together with tests for the presence of Escherichia coli, Staphylococcus aureus, Shigella, and Pseudomonas aeruginosa and Salmonella spp. %* The European Pharmacopoeia also specifies that E. coli and Salmonella spp. should be absent from herbal preparations..Materials of vegetable origin tend to show much higher levels of microbial contamination than synthetic products The allowed contamination level may also depend on the method of processing of the drug. The presence of fungi should be carefully investigated and/or monitored, since some common species produce toxins, especially aflatoxins. Aflatoxin-producing fungi sometimes build up during storage.Cont... %* Procedures for the determination of aflatoxin contamination in herbal drugs are published by the WHO. %* After a thorough clean-up procedure, TLC is used for confirmation. * Certain plant constituents are susceptible to chemical transformation by contaminating microorganisms.7. Determination of Pesticide Residues %* Herbal drugs are liable to contain pesticide residues, which accumulate from agricultural practices, such as spraying, treatment of soils during cultivation, and administering of fumigants during storage. * However, it may be desirable to test herbal drugs for broad groups in general, rather than for individual pesticides.Many pesticides contain chlorine in the molecule, which, can be measured by analysis of total organic chlorine. In an analogous way, insecticides containing phosphate can be detected by measuring total organic phosphorus. Samples of herbal material are extracted by a standard procedure, Impurities are removed by partition and/or adsorption, and individual pesticides are measured by GC, MS, or GC/MS residues in medicine.8. Determination of Radioactive Contamination e There are many sources of ionization radiation, including radionuclides, occurring in the environment. e Hence a certain degree of exposure is inevitable. e Dangerous contamination, however, may be the consequence of a nuclear accident.eltis serious depend on e The specific radionuclide, e The level of contamination, and e The quantity of the contaminant consumed. e Taking into account the quantity of herbal medicine normally consumed by an individual, they are unlikely to be a health risk. e Therefore, at present, no limits are proposed for radioactive contamination.9. Analytical Methods %* The quantitative determination of constituents has been made easy by recent developments in analytical instrumentation. * TLC, HPLC, GC, quantitative TLC (QTLC), and high-performance TLC (HPTLC) can determine the homogeneity of a plant extract.* Over-pressured layer chromatography (OPLC), infrared and UV-VIS spectrometry, MS, GC, liquid chromatography (LC) used alone, or in combinations such as GC/MS, LC/MS, and MS/MS, and nuclear magnetic resonance (NMR), are powerful tools, often used for standardization and to control the quality of both the raw material and the finished product. * The results from these sophisticated techniques provide a chemical fingerprint as to the nature of chemicals or impurities present in the plant or extract.