Chapter No. 1 Gene Chapter General ral Intr Introduc oduction tion Sem. 1, Second Professional By
Abdul Aleem Awan Lecturer , Pharmacy Department Hazara University Uni versity
Pharmacognosy Pharmac acog ogno nosy sy is der deriv ived ed fr from om two Gr Greek eek word wordss, • Pharm Pharmakon & Gnosis
• Pharmakon – means ‘drug’. • Gnosis – means ‘knowledge’. • In brief, Pharmacognosy means ‘knowledge of drugs’. It is a study of drugs that originate in the plant & animal
kingdoms. Pharmacognosy is a branch of pharmacy which deals with the basic resources of medicines from nature (plant & animal) and their uses as medicaments from ancient time to present day day..
Pharmacognosy Pharmac acog ogno nosy sy is der deriv ived ed fr from om two Gr Greek eek word wordss, • Pharm Pharmakon & Gnosis
• Pharmakon – means ‘drug’. • Gnosis – means ‘knowledge’. • In brief, Pharmacognosy means ‘knowledge of drugs’. It is a study of drugs that originate in the plant & animal
kingdoms. Pharmacognosy is a branch of pharmacy which deals with the basic resources of medicines from nature (plant & animal) and their uses as medicaments from ancient time to present day day..
Pharmacognosy Pharmacognosy may be defined as an important branch of Pharmacy which deals with the study of structural, physical, physic al, chemical, bioch biochemica emicall and senso sensory ry chara characters cters of natural natu ral drugs of plant and anima animall origin origin.. It also includ includes es a study of their history, distribution, cultivation, collection, ideentifica id cattion, prep epa aration, evaluation, preservation, use and commerce. pres esen entt ph phar arma maco cogn gnos osy y in invo volv lves es no nott on only ly th thee crude • At pr drugs but also their natural derivatives (pure compounds or constituents). leaf and its isolated glycoside, digitoxin digitoxin;; Rauwolfia • Digitalis leaf and root and its purified alkaloid, reserpine reserpine;; and thyroid gland with its extracted hormone, thyroxine thyroxine,, are all part of the subject matter of pharmacognosy pharmacognosy..
Pharmacognosy - History History of ph pha armacognosy is actua uallly the history of medicine that is medicinal plants.
Pre-history:
•
The first or beginning of pre-history on use of medicinal plants or herbs or animals, and the place where and how used were not well known, and those information were unwritten for a long time. As a result, the pre-history on herbs was almost lost.
•
How Ho wev ever er,, som omee in infform rmat atiion wa wass rec ecor orde ded d by oral oral transmission from generation to generation.
Pharmacognosy - History Written History: •
The written history has originated which was based on region, religion and culture etc.
The written history was divided into the following: 1.
The western medicine
2.
The Unani (Islam)
3.
The Ayurveda (Indian)
4.
The orient
5.
The Greek History
6.
The African System
Pharmacognosy - History
1. The western medicine: This is originated in Mesopotamia and Egypt. Mesopotamia is
considered as the first origin of human civilization. The Sumerians (peoples of ancient Mesopotamia) developed cuneiform tablet of herbal medicines. Those tablets are preserved in British museum. In Egypt, information had been written on paper – Papyrus
ebers (1600BC). It consisted of 800 prescriptions, mentioning 700 drugs. The first pharmacopoeia named London Pharmacopoeia was
published in 1618 and then British Pharmacopoeia was published in 1864.
Pharmacognosy - History
2. The Unani (Islam) • This herbal system was developed by Arabian Muslim Ibn Sina (980 – 1037 AD). He was a prince and ruler. He was a very brilliant pharmacist and physician who wrote a book – “Kitab-Al-Shifa”, means ‘Book of Healing’. • The book was written on Arabic language. This is a great contribution of Ibn Sina towards medical and pharmaceutical sciences.
Pharmacognosy - History
3. The Ayurveda Ayurveda (Indian, 2500-600 25 00-600 BC): Ayurveda is the term for traditional medicine of ancient India. The word “Ayur “Ayur” ” means ‘Life ‘Life’’ and “veda “veda” ” means ‘The ‘The study of of’’ that is “Study of Life”. Life”. The Ayurvedic writings were divided into three three systems: 1) Charaka Samhita ta,, 2) Sush shrruta Samhita and 3) Astang Ast anga a sam samhit hita. a. The oldest writing was Charaka Samhita (six to seven century before Christ). Thee bo Th book ok de desc scri ribe bess us uses es of man any y met etal alli licc dr drug ugss eg eg., ., iron, mercury, sulphur, copper etc with herbs.
Pharmacognosy - History
4. The orient (2700 BC): rig gin ina ate ted d fr fro om Chi Chines nese, e, Ja Japane panese se and This is ori Tibetians etc. The orient herbalism was very old (142 – 220 BC) and called “Kampo”. The written documents were made by the King ‘Shen Nung’ (2700 BC) and Shang (1766 – 1122 BC) etc. Shen Nung investigated medicinal value of several
herbs and written a book – “Pen T-Sao” or native herbal.
5. The Greek History:
Pharmacognosy - History
Some of the early naturalists, scientists and physicians who contributed enormously to the development of human knowledge about medicinal plants include following:
Hippocrates (Father of Medicine, 460-370 BC): He was the first natural doctor who utilized simple remedies such as vinegar, honey, herbs etc in healing. He is also known to have collected and identified a number of medicinal plants.
Aristotle (384-322 BC): He gave the philosophy of medicine. He listed more than 500 plants of medicinal importance.
Theophrastus Theophra stus (371-2 (371-287 87 BC): gave scientific basis of use of plants as medicine.
Galen Ga len (131-20 (131-200 0 AD): a Greek pharmacist-physician. He developed the methods of preparing and an d co com mpo poun undi ding ng med ediicin ines es by mec echa hani nica call mean ans. s. He wa wass th thee originator of the formulae for a cold cream. 10
Pharmacognosy - History
6. The African System (T (Tropical ropical Africa, North and South America): America): They keep information in their groups or tribes.
The information transmitted from one generation to another. Th Thes esee re regi gion onss ar aree ri rich ches estt so sour urce cess of med edic icin inal al
plants and needs to explore for new drug discovery.
Scope of Pharmacognosy Pharmacognosy deals primarily with information on the sources and constituents of natural drugs. 1.
Primary source of medicines (from ancient time to present day), for example – hyoscine, morphine, ergotamine, ouabain etc.
2.
Providing Template/guide for the discovery of new drugs, for example – Pathidine (analgesic drug) designed from morphine.
Terms & Phrase used in Pharmacognosy
Terminology
Drug Standard dictionaries define drug as “an original, simple medicinal substance, organic or inorganic, used by itself or as an ingredient in medicine”. According to WHO’s definition – “any substance used in a pharmaceutical product that is intended to modify or explore physiological systems or pathological states for the benefit of the recipient”. Pharmaceutical product/Medicine means “a dosage form (tablet/capsule/syrup/Inj - IV/IM) containing one or more drugs along with other substances included during the manufacturing process”.
Application of Drug •
Prevention of a disease : for example, vaccine.
•
Fight against an infection: for example, antibiotics.
•
Temporary blocking of a normal function: for example, general & local anesthetics
•
Detoxification of the body: for example, antidotes.
•
Diagnostic agents: for example, radioisotopes.
•
Correction of dysfunction: for example, cardiotonics (eg, digoxin) for the treatment of congestive heart failure.
•
Correction of hyperfuntion: for example, Rauwolfia root (eg., reserpine) for the treatment of hypertension.
Terminology
Crude Drug: The term “Crude”, as used in relation to natural products. A crude drug is a natural drug of plant or animal origin which has undergone no treatment other than collection and drying, that is, the quality or appearance of the drug has not been advanced in value or improved in condition by any physical or chemical treatment. For example: Digitalis leaf, Rauwolfia root etc.
Terminology
Indigenous vs Naturalized Indigenous : Plants growing in their native countries are said to be indigenous to those regions. For example: Aconite ( Aconitum napellus) in the mountainous region of Europe. It is highly poisonous used as diuretic in Homeopathy preparation Naturalized: Plants are said to be naturalized when they grow in a foreign land or in a locality other than their native homes. For example: Datura ( Datura stramonium) which was introduced into the USA from Europe.
Official Books It provides guideline for the manufacturing, quality control, packaging, storage, dose regimen, indication, contraindication etc of different pharmaceutical products/medicine for the treatment of diseases. • USP – United States Pharmacopoeia
• BP – British Pharmacopoeia • NF – National Formulary • BNF – British National Formulary • BDNF – Bangladesh National Formulary • BPC – British Pharmaceutical Codex • Martin Dale Extra Pharmacopoeia • Materia Medica • Physician’s Index • Goodman’s & Gilmann’s: The Pharmacological Basis of
Official vs Unofficial vs Nonofficial drug
Terminology
Official drug: Any drug (crude or prepared) which is included in pharmacopoea or in national formulary or in recognized books is called an ‘official drug’. For example: quinine, morphine, codeine, paracetamol are included in BP, USP, NF and so on.
Unofficial drug: A drug which has been recognized earlier in the pharmacopoeia or in national formulary or in recognized books but not found in the current issue is designated as an ‘unofficial drug’. Those substances were excluded from the recognized books due to their severe toxic effects on humans. For example: Sucralfate (hyperacidity), mercurial compounds (diuretics), benzoic acid
Terminology Official vs Unofficial vs Nonofficial drug
Nonofficial drug Substance that has never been appeared in either of the official books may be called nonoffical. Such types of compounds may be published in current journals having proven clinical value, but we do not know about their side effects. For example - Curcumine (sinusitis), etc.
Terminology
Extractive The crude mixtures of chemical constituents that are removed from plants or animals by various extraction processes are called extractives or derivatives.
Secondary metabolites These are substances synthesized or produced as by-products by plants during their metabolic activities. Apparently they are of no primary use to plants. They are therefore also regarded as ‘waste products of metabolism, which are usually accumulated in some parts of the plant and are physiologically active on living organisms.
Terminology
Monograph The descriptive material pertaining to any drug, therapeutic agent included in the pharmacopoeia is known as the monograph. The monograph of a drug includes the following information on the drug: official
title,
synonyms,
definition,
description,
collection or preparation, identity tests, tests for adulterants, method of assay, storage, uses and doses.
Monograph of Trigonella foenum-graecum (Family: Papilionacacae) Common name: Fenugreek (Eng.), Methi (Bengali) Cultivation: It is cultivated in different area of Bangladesh, India, Pakistan, Middle
East, Africa. Description: The Latin species name foenum-graecum means ‘Greek hay’, which
is a dried plant's (leaves or seeds) and has a strong hay-like scent. It has a strong, pleasant and a peculiar odor and grows best in well-drained soils with a low rainfall into brownish- yellow rhombic shape seeds. Parts used: Ripe, dried seeds Chemical constituents:
Seeds are rich in mucilage (maily galactomannans),
fixed oil, fatty acids and protein. They also contain alkaloids, saponine, glycosides etc. Uses:
Seeds are diuretics, astringent. They are popularly used in the treatment
of loss of appetite, weight loss, menstrual disorder. Also used in hypertension, diabetes, etc. It lowers TG, cholesterol, LDL.
Fenugreek (Kasuri Methi)
Fenugreek seeds
Dried Fenugreek
Fenugreek with flowers
Fenugreek Powder
Pharmacognosy & Modern Medicine Simultaneous
chemistry,
advancement biochemistry,
in
the
field
biosynthesis
of and
pharmacology has developed pharmacognosy. Various active compounds have been isolated from
plants which are used in modern medicine. With
the
advancement
of synthetic
organic
chemistry most of the active constituents of plants have been synthesized. 100s of plants are used in modern medicine in
various parts of the world.
25
Pharmacognosy & Modern Medicine
Important active constituents of plants used in medicine Active constituents
Plants
Pharmacological activity
Morphine, Codeine,
Papaver somniferum L.
Sedative, smooth muscle
Papaverine Quinine, Quinidine
relaxant
Cinchona sp.
Antimalarial, antiarrthythmic
Hyoscine, Atropine
Datura sp.,
Parasympatholytic
Digitoxin, Digoxin
Digitalis lanata
Cardiotonic
Reserpine, Rescinamine
Rauwolfia sp.
Hypotensive, vasodialator
Vincristine, Vinblastin
Catharanthus roseus
Anticancer
Pharmacognosy & Modern Medicine
Important active constituents of plants used in medicine Active constituents Plants
Pharmacological activity
Caffeine
Camellia sinenssis
CNS stimulant
Cocaine
Erythroxylum coca
Anaesthetic
Ephedrine
Ephedra sp.
Sympathomimetic
Pilocarpine
Pilocarpus jaborandi
Parasympathomimetic
Ergometrine
Claviceps purpurea
Oxytocic
Ergotamine
Vasoconstrictor
Ergotoxine
Vasodialator
Pharmacognosy & Modern Medicine
Important active constituents of plants used in medicine Active constituents
Plants
Pharmacological activity
Psyllium mucilage
Plantago ovata
Laxative
Sennosides
Cassia
Laxative
angustifolia Theophylline
Caffea arabica
CNS stimulant Diuretic
Steroid hormones
Solanum sp.
Anti-inflammatory, antiarthriytic
Application of Pharmacognosy •
Plants always provide novel molecular structure, which played important role for the molecular design and development of novel potent, less toxic or nontoxic drugs e.g. natural morphine has got analgesic & narcotic effect but meperidine a synthetic drug originates from morphine basic skeleton is nonnarcotic.
•
Plant & animal products give potential biological effect without any undesirable effects.
•
Plant & animal products can be taken with very ease.
Limitation of Pharmacognosy Drugs obtained from natural sources have a variety of limitations. The majors are;
•
A natural compound may be highly active but usually this is associated with high toxicity problem, ex- the toxic and therapeutic dose of digitalis are very close which create serious problem to use this medicine by the patient alone.
•
Some compounds are found in nature that give beneficial pharmacological actions but their potencies are too low to be employed therapeutically.
•
The yield of active natural products may be very low and thus the production cost of those drugs will be very high
•
The source of a natural drug may be very limited with respect to geography, season and climate etc.
Sources of Medicaments •
At present the prime source of modern or allopathic medicines is synthesis in the laboratory by organic chemist.
•
Only a few of compounds are isolated from plants, which cannot be replaced by synthetic method.
•
For example: morphine isolated from Papaver somniferum; vincristin & vinblastin (anticancer drug) from Vinca rosea, the most potent anticancer drug taxol from Texus brevifolia; the constituents of digitalis cannot be properly replaced by any synthetic drug like quinidine which is used for the treatment of arrhythmia.
Classification of Drugs In pharmacognosy, drugs may be classified according to -
1.
Their morphology
2.
The taxonomy of the plants and animals from which they are obtained
3.
Their therapeutic/ pharmacological application
4.
Their chemical constituents or active principles. Each of these methods of classification has advantages and disadvantages.
1. Morphological classification •
Classification of Drugs
In this system, the drugs are grouped according to the part of the plants, such as roots, leaves, stems, barks, flowers, seeds etc.
•
The drugs obtained from the direct parts of the plants are called as organized drugs. They are made up of whole plants or any parts derived from them. eg., Root – Rauwolfia, aconite, ginger; Bark – Cinnamon, Cinchona Fruit – Amla, Bahera, Capsicum, Leaf – Digitalis, Senna, Tulsi, coca; Wood – Sandal wood.
•
The drugs which are prepared from plants by some intermediate physical process such as incision, drying or extraction with a solvent are called unorganized drugs, eg., Dried juice (Aloe juice), Dried extract (agar), Dried latex (Opium latex), Honey, Beewax etc. The main drawback of morphological classification is that there is no corelation of chemical constituents with the therapeutic actions.
Classification of Drugs
2. Taxonomical classification •
In this system crude drugs are arranged according to the natural groups (e.g. Families) of their source.
•
For example: all the drugs obtained from Solanaceae are grouped together as Solanaceous drugs.
•
Tropane
alkaloids
are
the
main
constituents
of
Solanaceous drugs. Family
Drugs
Solanaceae
Solanaceous drugs. eg. Tropane alkaloids
Umbelliferae
Umbelliferous drugs. eg., 34 volatile oils
Classification of Drugs
3. Pharmacological classification •
In pharmacological classification the drugs are grouped according to their therapeutic use.
•
For example cardiotonic drug include digitalis, purgative drugs include castrol oil. Pharmacological action
Drugs
Anticancer
Vinca
Analgesic
Opium, cannabis
Purgatives
Senna, Aloe, Castrol oil, Plantago husk
Cardiotonic
Digitalis, strophanthus
Tranquillizer
Rauwolfia root
Anti-inflammatory
Tumeric, colchicum
The main drawback of this classification is that a drug can be placed in various classes according to its therapeutic use. For example: Cinchona
Classification of Drugs
4. Chemical classification
• The biological activity of a drug is due to the presence of certain chemical constituents in the drug.
• Plants
and
animals
synthesize
chemical
compounds such as carbohydrates, protein, fat, volatile oils, alkaloids, resin etc.
• The chemical classification of drugs is dependent upon
the
grouping
of
drugs
with identical
Classification of Drugs
Chemical classification of drugs Chemical constituents 1.
Drugs
Carbohydrates a) Monosaccharidase
- Dextrose, fructose, galactose
b) Disaccharide
- Sucrose, Lactose, Maltose
c) Polysaccharide
- Starch
Gum
- Acacia, Tragacanth
Mucilages
- Plantago seed
Cellulose
- Cotton
2. Glycosides a) Cardiac
- Digitalis, strophanthus
b) Anthraquinone
- Aloe, Cascara, senna
c) Saponins
- Arjuna
d) Cyanophore
- Wild cherry bark
3. Tanins
Amla, Bohera, Ashoka bark
4. Volatile oil
Clove oil, rose oil, peppermint oil, tulsi etc
5. Lipids a) Fixed oils & fats
- Olive oil, castor oil, coconut oil etc
b) Waxes
- Bees wax
Classification of Drugs
Chemical classification of drugs Chemical constituents
Drugs
6. Resins
ginger, capsicum etc.
7. Alkaloids a) Pyridine & piperidine
a) Nicotiana, areca nut
b) Tropane
b) Coca, Belladonna, Datura
c) Quinoline
c) Cinchona
d) Isoquinoline
d) Opium, Ipecac
e) Indole
e) Ergot, Nuxvomica, Rauwolfia, catharanthus, Physostigma
f) Steroidal
f) Kurchi
g) Purine
g) Tea, Coffee
8. Protein
Gelatin, gluten etc
9. Vitamins
Thiamine (B1), Riboflavin (B2), Ascorbic acid etc
10. Antibiotics
Penicillin, streptomycin, tetracycline etc
11. Hormones
Adrenaline, thyroxine etc
Evaluation of Drugs • A natural substance is considered as food if it fills stomach in every day life without any harmful effect.
• A substance becomes a drug if it changes a pathological or disease state of human/ animal to normal physiological condition having no undesirable effect in specific dose.
• A long-term studies (chemical, biological and physical etc) are required to establish whether a substance will be considered as drug or food or eliminate for consumption. Those studies are referred to as evaluation. Evaluation of drug means – • Identification • Determination of quality • Determination of purity
Identification Cultivation The identification can be established by careful observational study
of the collected drug, and then compared with authentic specimen by the collector. Therefore, for proper identification of a drug from plant or animal
sources, a collector must be educated about plant taxonomy and very much experienced with his/her job. Therefore, drugs from plants/animals are identified by –
o
A qualified, specialized & experienced person
o
Comparison with the authentic sample specimen.
In every country, there is a national herbarium where most of plants
specimen are preserved. A number of specialists are working on plant identification there.
Quality •
The word “quality” refers to the intrinsic value of the drug, i.e., the
amount of medicinal principles or active constituents
present. These principles are classified as carbohydrate, alkaloid, glycoside, volatile oil, lipid, antibiotics and steroids etc.
•
A high grade of quality in a drug is of primary importance. An effort should be made to obtain and maintain high quality.
•
To maintain high quality products one should do the following:
1. Select proper source (wild or cultivated) 2. Appropriate time of collection 3. Collection of required parts of plants (bark, leaf, stem, rhizome, root) 4. Preparation of the collected drug by proper cleaning, drying. 5. Proper preservation to avoid contamination by microorganisms and moisture, heat, air and light.
Purity • The purity of drug can be achieved by – 1. Proper identification 2. Quality assurance.
Evaluation Method •
The evaluation of a drug involves a number of methods, which may be classified as follows:
1. Organoleptic 2. Microscopic 3. Biological 4. Chemical 5. Physical
1. Organoleptic evaluation of drug • Organoleptic evaluation means the study of a drug with the help of organs of sense.
• It
includes
any
drug’s
macroscopic
or
external
appearance, color, odor, taste & sounds of its fracture etc.
• The macroscopic or external characteristic of a drug may be divided into 7 headings 1. Shape 2. Size 3. Color 4. Internal color 5. Fracture 6. Odor
2. Microscopic evaluation of drug
Microscopic evaluation of drug can be done in the laboratory by the use of microscopes and utilizes various microscopic characters of the drugs, such as types and arrangement of various cells and tissues.
3. Chemical evaluation of drug
• Chemical
evaluation
of
drugs
involves
both
qualitative and quantitative determination of their active principles.
• In this method characteristic qualitative chemical tests are employed to identify crude drugs and their constituents.
4. Biological evaluation of drug
• The biological evaluation of crude drugs is very useful in determining the pharmacological activity of the drug.
• Since living organism or their isolated living tissues are used, this method is also called the biological method or bioassay.
• Many drugs, particularly the antibiotics, toxins and toxoids and also vitamins are assayed by this method.
5. Physical evaluation of drug
The
physical
evaluation
of
crude
drugs
is
accomplished by the determination of various physical characteristics
using
various
physico-chemical
techniques, for example, specific gravity (of fats and volatile oils), melting points (of alkaloids), optical rotation (of alkaloid and volatile oils), etc.
Preparation of Drugs for Commercial Market • Following are different steps performed for preparation of drugs for market.
– Collection – Harvesting – Drying – Garbling – Packaging, storage, and preservation
1. Collection Collection of drugs from cultivated plants always insures a true natural source and a reliable product. This may, or may not, be the case when drugs are collected from wild plants. Carelessness or ignorance on the part of the collector can result in complete or partial substitution. This is especially true when drugs arc difficult to collect or the natural source is scarce. Many drugs are collected from wild plants sometimes on a fairly extensive scale (tragacanth, senna) when collection is the vocation of the gatherer, and sometimes on a limited scale when collection is an avocation (podophyllum, hydrastis). Because drugs come from all over the world, collection areas are almost universal, and collectors may vary from uneducated natives to highly skilled botanists.
1. Collection contd.. Time of collecting: The proper time of collecting is particularly important because the nature and quantity of constituents vary greatly in some species according to the season. The most advantageous collection time is when the part of the plant that constitutes the drug is highest in its content of active principles and when the material will dry to give the maximum quality and appearance.
2. Harvesting
The mode of harvesting varies with each drug produced and with the pharmaceutical requirements of each drug. Some drugs may be collected by hand labor; however, when the cost of labor is an important factor, the use of mechanical devices is often more successful in economic production of the drug. With some drugs, where the skillful selection of plant parts is an important factor (digitalis), mechanical devices cannot replace hand labor.
3. Drying
By drying the plant material, one removes sufficient moisture to ensure good keeping qualities and to prevent molding, the action of enzymes, the action of bacteria, and chemicals or other possible changes. Drying fixes the constituents, facilitates grinding and milling, and converts the drug into a more convenient form for commercial handling. Proper and successful drying involves two main principles: Control of temperature
and Regulation of air flow.
3. Drying contd.. Control of the drying operation is determined by the nature of the material to be dried and by the desired appearance of the finished product. The plant material can be dried either by the sun or by the use of artificial heat. With some natural products, such as vanilla, processes of fermentation or sweating are necessary to bring about changes in the constituents. Such drugs require special drying processes, usually called "curing."
4. Garbling Garbling is the final step in the preparation of a crude drug. Garbling consists of the removal of extraneous matter, such as other parts of the plant, dirt, and added adulterants. This step is done to some extent during collection, but should be carried out after the drug is dried and before the drug is baled or packaged. Although garbling may be done by mechanical means in some cases, it is usually a semiskilled operation.
5: Packaging, storage, and preservation The packaging of drugs depends on their final disposition. In commerce, if transportation, storage, and ultimate use for manufacturing purposes are involved, it is customary to choose the type of packaging that provides ample protection to the drug and gives economy of space. Leaf and herb material is usually baled with power balers into a solid compact mass that is then sewn into a burlap cover. Senna leaves from India come in bales of 400 lb; stramonium from Argentina in bales of 700 lb. Drugs that are likely to deteriorate from absorbed moisture (digitalis, ergot) are packed in moisture-proof cans. Gums, resins, and extracts are shipped in barrels, boxes, or casks.
5: Packaging, storage, and preservation contd… Proper storage and preservation are important factors in maintaining a high degree of quality of the drug. Hard-packed bales, barks and resinous drugs usually reabsorb little moisture. But leaf, herb and root drugs that are not well packed tend to absorb amounts of moisture that reach 10, 15, or even 30% of the weight of the drug. Excessive moisture not only increases the weight of the drug, thus reducing the %age of active constituents, but also favors enzymatic activity and facilitates fungal growth. Light adversely affects drugs that are highly colored, rendering them unattractive and possibly causing undesirable changes in constituents. The oxygen of the air increases oxidation of the constituents of drugs, especially when oxidases are present. Therefore, the warehouse should be cool, dark, and well ventilated with dry
5: Packaging, storage, and preservation contd… The protection of drugs against attacks by insects must not be overlooked. The insects that infest vegetable drugs belong chiefly to the orders Lepidoptera , Coleoptera, and Diptera. For destruction of insects and prevention of their attacks, a number of methods have been employed. The simplest & the most efficient method is to expose the drug to a temperature of 65°C which not only prevents insect attacks, but also many other forms of deterioration. For the fumigation of large lots of crude drugs, such as those stored in warehouses and manufacturing plants, the use of methyl bromide has met with considerable success. Small lots of drugs may readily be stored in tight, lightresistant containers e.g. tin cans, covered metal bins, or amber glass containers.
5: Packaging, storage, and preservation contd… Drugs should not be stored in wooden boxes or in drawers and never in paper bags. Not only is deterioration hastened, but odors are communicated from one drug to another, attacks by insects are facilitated, and destruction by mice and rats may occur. If drugs in small quantities are stored in tight containers, insect attack can he controlled by adding to the container a few drops of chloroform or CCl 4 from time to time. In the case of digitalis and ergot, whose low moisture content must be maintained at all times, the insertion of a suitable cartridge or device containing a non-liquefying, inert, dehydrating substance may be introduced into the tight container.
5: Packaging, storage, and preservation contd… Because high temperatures accelerate all chemical reactions, including those involved in deterioration, drugs must always be stored at as low temperature as possible. The ideal temperature is just above freezing, but since this is impractical in most cases, the warehouse or other storage place should be as cool as possible. Certain drugs such as the biologics, must be stored at a temperature between 2 and 8ċ .
Animal Drugs Animal drugs are produced from wild or domesticated animals. Wild animals must be hunted (whale, musk deer) or fished for (cod and halibut), and thus, in a sense, their collection parallels the collection of vegetable drugs. Many animal drugs, however, are produced from domesticated animals &, therefore, correspond to the cultivated vegetable drugs. When drugs consist of insects, the drugs are either collected from wild insects (cantharides) or definite attempts are made to cultivate them, i.e., to furnish the insects with food and shelter and to maintain optimum conditions for their propagation (honeybee).
Animal Drugs contd.. Drugs such as lanolin and milk products, as well as hormones, endocrine products, and some enzymes, are obtained from domesticated pigs, sheep, or cattle. The slaughterhouse is the usual source of glandular products and enzymes, and the larger packing establishments have departments for the recovery and refinement of these therapeutic agents and pharmaceuticals. Processing and purification of the animal drugs vary with the individual drug.
Adulteration of Crude Drug • The term 'adulteration' or debasement of an article covers a number
of
conditions,
which
may
be
deliberate
or
accidental. Usually in crude drugs, this practice includes substitution of the original crude drugs partially or fully with other substances which is either free from or inferior in therapeutic and chemical properties.
1) Inferiority is a natural substandard condition (e.g. where a crop is taken whose natural constituent is below the minimum standard for that particular drug) which can be avoided by more careful selection of the plant material.
Adulteration of Crude Drug contd.. 2) Spoilage is a substandard condition produced by microbial or other pest infestation, which makes a product unfit for consumption, which can be avoided by careful attention to the drying, and storage conditions.
3) Deterioration is an impairment of the quality or value of an article due to destruction or abstraction of valuable constituents by bad treatment or aging or to the deliberate extraction of the constituents and the sale of the residue as the original drugs.
4) Admixture is the addition of one article to another through accident, ignorance or carelessness e.g. inclusion of soil on an underground organ or the co-collection of two similar species.
Adulteration of Crude Drug contd.. 5) Sophistication is the deliberate addition of spurious or inferior material with intent to defraud; such materials are carefully produced and may appear at first sight to be genuine e.g. powder ginger may be diluted with starch with addition of little coloring material to give the correct shade of yellow color.
6) Substitution is the addition of an entirely different article in place of that which is required e.g. supply of cheap cottonseed oil in place of olive oil.
Types of Adulteration Of Crude Drugs Different methods used for adulteration may be grouped as follows: 1) Substitution with inferior commercial varieties. 2)
Adulteration by artificially manufactured substitutes.
3) Substitution by exhausted drugs. 4)
Substitution by superficially similar but cheaper natural substances.
5) Adulteration by addition of worthless heavy materials. 6) Addition of synthetic principles. 7) Usage of vegetative matter from the same plant.
Types of Adulteration Of Crude Drugs contd.. 1. Substitution with Inferior Commercial Varieties Due to morphological resemblance to the authentic drugs, different inferior commercial varieties are used as adulterant which may or may not have any chemical or therapeutic potential as that original natural drug e.g. Arabian Senna (Cassia angustifolia), dog Senna (Cassia obovata ) and avaram ( Cassia auriculata) have been used to adulterate Senna (Cassia senna); Japanese ginger ( Zingiber mioga) to adulterate medicinal ginger ( Zingiber officinale ).
2. Adulteration by Artificially Manufactured Substitutes To provide the general form and appearance of various drugs, some materials are artificially manufactured and are used as substitute of the original one, e.g. artificial invert sugar for honey; paraffin wax after yellow coloration substituted for bees wax.
Types of Adulteration Of Crude Drugs contd.. 3. Substitution by Exhausted Drugs Here the same plant material is mixed which is having no active medicinal components as they have already been extracted out. This practice is most common in case of volatile oil containing materials like clove, fennel etc., where the dried exhausted material resembles the same like original drug (similarly with drugs like Cascara sagrada and ginger). Sometimes when coloring matters have been extracted or removed during exhaustion, the residue is recolored with artificial dyes as is done with saffron and red rose petals.
Types of Adulteration Of Crude Drugs contd.. 4.
Substitution by Superficially Similar but Cheaper Natural Substances Usually here the adulterated product has no relation with the genuine article, may or may not have any therapeutic or chemical component desired, e.g. leaves of species Ailanthus are substituted for belladonna, senna, mint etc.; Leaves of Phytolacca and Scopolia for belladona; Leaves of Xanthium for stramonium and dandelion for henbane; Indian dill with European dill or caraway etc.
5.
Adulteration by Addition of Worthless Heavy Materials A large mass of stone mixed with Liquorice root, pieces of limestone are found in asafoetida and lead shot has occurred in pieces of opium etc.
Types of Adulteration Of Crude Drugs contd.. 6.
Addition of Synthetic Principles Sometimes to fortify inferior natural products, synthetic principles are added e.g. adding citral to oil of lemon; benzyl benzoate to balsam of Peru etc.
7.
Usage of Vegetative Matter from the Same Plant This is done by mixing adventitious matters or naturally occurring with the drug in excessive amount or parts of plant other than that which constitutes the drugs. For example liver warts and epiphytes growing in bark portion are mixed with Cascara or Cinchona ; stems of buchu are sometimes cut into short lengths and added to the drug.
Deterioration of Crude Drugs •
Besides being adulterated by different means as discussed earlier, the crude drugs are prone to deterioration on storage. 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. Several factors are to be considered for the detrimental effects on the stored products.
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Several primary environmental factors relating to storage can produce detrimental effects on stored products e.g. 1)
Light,
2)
Moisture / humidity,
3)
Temperature &
4)
Oxygen etc.
But more deterioration usually results from a combination of these factors, which leads to the development of living organism including
Primary Factors for Deterioration 1.
Light Photo-decomposition occurs with santonin, the principal constituents of wormseed, which on exposure to light darkens and eventually becomes black. In general, drugs should be protected by suitable light-proof wrapping or by the use of amber colour containers. Powdered rhubarb stored in clear glass jars rapidly changes as the exposed surfaces turning from yellow to more reddish colour. For these detrimental effects, WHO has specified that medicinal plant materials requiring protection from light should be maintained in a light resistant container that shields the contents from the effects of light. Alternatively, the container maybe placed inside a suitable light resistant (opaque) covering and/or stored in a dark place.
Primary Factors for Deterioration contd.. 2. Moisture/Humidity Moisture present in drugs depends largely upon the amount of moisture in the atmosphere, which is usually expressed in the terms of humidity. When the atmosphere is completely saturated, the humidity is 100%, when half saturated it is 50% and so on. Drugs stored in non-airtight containers are termed air-dry and contain about 10-12% of water depending on the humidity of the atmosphere. This amount of water is sufficient to activate the enzymes present in some dried plant materials, such as Digitalis and bring about the decomposition of the active glycosides. Such drug should therefore be stored with a dehydrating agent or in sealed containers immediately after drying. Squill contains a hygroscopic mucilage and the powder there from, if exposed to the atmosphere, will pickup moisture and become a sticky mass. Therefore strict humidity control is necessary while storing; low moisture may be maintained, if necessary by the use of desiccant in the container provided that direct contact with the product is avoided.
Primary Factors for Deterioration contd.. 3.
Temperature It has a marked effect which is sometime unsuspected. Many enzymatic changes in the plant secondary metabolites proceed more rapidly at the slightly raised temperature up to about 45°C. Obviously those drugs containing volatile constituents in unprotected structures, e.g. plants belonging to Labiatae family and the petals of rose and chamomile all loose oil with an increase in temperature. Absorbent cotton wool contains a small amount of fatty material which is the residual component from the natural fiber. At a raised temperature these molecules become re-oriented, spreading themselves over the surface of the fiber to form an impervious layer. Thus cotton wool, once fully absorbent will gradually become completely non-absorbent because of the effect of temperature.
Primary Factors for Deterioration contd.. 4.
Air Oxidation Direct oxidation of the constituents of crude drug is sometime brought about by the oxygen of the air, e.g. Linseed oil rapidly become resinified as like the oil of Turpentine and oil of Lemon. Usually this conversion is applied to the essential oil with terpenoid derivatives and we can find the resinous deposit build-up around the stoppers used in dispensing bottle containing this oil. Beside this, the rancidification of fixed oils e.g. cod-liver oil, which involves the formation of unstable peroxides, is also an oxidative process. Thus, these types of materials require storage in a well-filled, airtight container.
Secondary Factors for Deterioration •
Living organisms usually develop in stored drugs where the conditions are satisfactory for them. From a hygienic point of view, such contaminated material should be destroyed irrespective of whether or not the active principles of drug have been effected. The more common of such organisms belongs to the groups of bacteria, moulds, mites, nematodes, worms, insects etc. 1)
Bacteria and Moulds
2)
Mites and Nematode Worms
3)
Insects/Moths
4)
Coleoptera or Beetles
Secondary Factors for Deterioration contd.. 1.
Bacteria and Moulds Dried herbs are particularly liable to be contaminated with the spores of the bacteria and moulds, which are always present in the air. Under satisfactory storage conditions their presence causes no problem, but it is generally accepted that the viable count permissible for crude drugs should be the same as that for the food stuff . The effect produced by bacteria are not always very visible with the exception of some chromogenic species of bacteria, e.g. Bacillus prodigious, which produces red patches in starchy materials. However, bacterial growth is usually accompanied by the crude drug by growth of moulds whose presence is quickly evident by the characteristic smell and by the mass of clinging particles entrapped in the mycelial hyphae.
Secondary Factors for Deterioration contd.. Dusty cotton wool, which is formed by bacterial attack causing the trichomes to break into short length, rendered it to be very brittle. In order to identify a particular mould or bacteria, which is proliferating in a stored product, it is necessary to culture it on a suitable medium with a view to obtain fruiting bodies for examination. However, if the drug to be examined is infested rapidly, then it may be possible to make microscopic preparation directly from the sample. Usually the moulds encountered with poorly stored drugs include the genera Mucor (e.g. grey mould, M. mused), Rhizopus (e.g. black mould, R. nigricans), Penicillium (e.g. blue mould, P. glaucum), Aspergillus (e.g. green mould, A. repens) and Saccharomyces.
Secondary Factors for Deterioration contd.. 2.
Mites and Nematode Worms If found in stored drugs, mites are usually present in countless numbers upto 1.0 mm in length. Different mites found usually include Tyroglyphces siro (Cheese mite); Aleurobius farinae (Flour mite) and Glycyphagus spinipes (Cantharides mite). All these mites can be examined microscopically by clearing the sample of powder containing them with chloral hydrate reagent. The best known examples of nematode worms are "Vinegar eel" Turbatrix aceti, Anguillula aceti, Anguina tritici which are found in wheat flour or in the crude drug containing starchy materials. These worms are visible to the unaided eye as minute threads continually curling and twisting in the medium they inhabit.
Secondary Factors for Deterioration contd.. 3.
Insects/Moths A few species of the Lepidiptera attack the stored crude drugs and cause damage at the larval stage, where the infestation can spread rapidly due to the mobility of the adults. The moths involved are unspectacular in appearance, 22-30 mm in length with off-white wings e.g. Ephestia kuehniella (Flour moth); E. ellutella (Cocoa moth). Besides this some other insects, cockroaches, ants and others are sometimes found to cause deterioration to the stored products.
4.
Coleoptera or Beetles These are the insects that constitute the largest order of the animal kingdom comprising about 2,50,000, species of which about 600 have been found to be associated with stored food product or drugs.
Stegobium paniceum is one beetle, which is found in many drugs including gentian, liquorice and rhubarb as well as leafy drugs and seeds. Belonging to the same family is Lasioderma serricorne (tobacco or cigar beetle) which is reddish brown in colour, 2 to 2.5 mm in length
Control Measures for Deterioration •
The container used for storage and its closure must not interact physically or chemically with the material within in any way which would alter its composition. A well closed container must protect the contents from extraneous matter or from loss of the material while handling and a tightly closed container must protect the material from efflorescence, deliquescence or evaporation under normal condition of handling or storage. Storage area should be kept clean and spillages not allowed to enter cracks or in accessible crevices. Periodic spraying of the premises with insecticides will help to prevent the spread of infestation.
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The principles, which apply to the control of infestation in warehouses, are equally applicable to small-scale storage. Good house keeping is utmost essential. Each stock should be inspected regularly and the material found to be contaminated is best to be destroyed by burning. In this respect a quick turn over to eliminate the effects of deterioration due to both the primary and secondary factors as mentioned above are desirable.
