QUALITY CONTROL OF CRUDE DRUGS EVALUATION OF CRUDE DRUGS .pptx

QUALITY CONTROL OF CRUDE DRUGS EVALUATION OF CRUDE DRUGS

1. Quality Control Of Herbal Drugs: Evaluation Of Herbal Drugs

2. INTRODUCTION Quality control of crude drugs material, plant preparations and finished products Stability assessment and shelf life Safety assessment; documentation of safety based on experience or toxicological studies Assessment of efficacy by pharmacological information and biological activity evaluations

3. Definition of quality control Quality control for efficacy and safety of herbal products is of paramount importance. Quality can be defined as the status of a drug that is determined by identity, purity, content, and other chemical, physical, or biological properties, or by the manufacturing processes. Quality control is a term that refers to processes involved in maintaining the quality and validity of a manufactured product. In general , all medicines, whether they are of synthetic or of plant origin, should fulfill the basic requirements of being efficacious and safe, and this can be achieved by suitable clinical trials

4. In general, quality control is based on three important pharmacopoeial definitions: Identity: Is the herb the one it should be? Purity: Are there contaminants, e.g., in the form of other herbs which should not be there? Content or assay: Is the content of active constituents within the defined limits?

5. Identity can be achieved by macro- and microscopical examinations. Voucher specimens are reliable reference sources. Outbreaks of diseases among plants may result in changes to the physical appearance of the plant and lead to incorrect identification. At times an incorrect botanical quality with respect to the labeling can be a problem. For example, in the 1990s, a South American product labeled as “Paraguay Tea” was associated with an outbreak of anticholinergic poisoning in New York. Subsequent chemical analysis revealed the presence of a class of constituents that was different from the metabolites- caffeine, tannin normally found in the plant from which Paraguay tea is made.

6. Purity is closely linked with the safe use of drugs and deals with factors such ash values, contaminants (e.g. foreign matter in the form of other herbs), and heavy metals. However, due to the application of improved analytical methods, modern purity evaluation also includes microbial contamination, aflatoxins , radioactivity, and pesticide residues. Analytical methods such as photometric analysis, thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and gas chromatography (GC) can be employed in order to establish the constant composition of herbal preparations.

7. Content or assay is the most difficult area of quality control to perform, since in most herbal drugs the active constituents are not known. Sometimes markers can be used. In all other cases, 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. The choice of the extracting solvent depends on the nature of the compounds involved, and might be deduced from the traditional uses . For example, when a herbal drug is used to make a tea, the hot water extractable matter, expressed as milligrams per gram of air-dried material, may serve this purpose.

8. Strict guidelines have to be followed for the successful production of a quality herbal drug. Among them are proper botanical identification , phytochemical screening and standardization .

9. STANDARDISATION Standardization of drug means “Confirmation of its identity and determination of its quality and purity, and detection of nature of adulterant by various parameters like morphological, microscopical , physical, chemical and biological observations.”

10. Crude Dugs Natural origin-Plants, animals, minerals, microbes, marine, etc. Direct parts or exudates or products Unprocessed one Raw forms O nly collected, dried, storage and packaging. Examples:

11. Definition of Drug evaluation Drug evaluation may be defined as the determination of identity, purity and quality of a drug. Identity: Identification of biological source of the drug. Purity: The extract of foreign organic material present in a crude drug. Quality: The quantity of the active constituents present.

12. Importance of evaluation of crude drugs To find out the standard and substandard drugs To check or to report the presence of impurities, substituention and adulteration, as result of careless, ignorance and fraud Determination of biochemical variation in the drugs Identification of deterioration due to treatment and storage To avoid the harmful effects getting after consumption of crude drugs

13. Methods of drug evaluation

14. 1. Morphology/ Organoleptic Evaluation This refers to drug evaluation by means our organs of sense and includes other sensory organs like odour , colour , taste and texture. It includes the study of morphology and other sensory characters.

15. Study of Gross Morphology: It includes the visual examination of drug. These drugs are classified into the following groups. Barks Underground structures Leaves Flowers Fruits Seeds Herbs

16. Barks: It includes all the tissues in a woody stem outside the interfascicular cambium which constitutes to the drug. Barks are collected from the trunk or branches of the trees a narrow strips. During drying the drug, it undergoes unequal contractions and assumes different shapes. Example: Cinnamon, Cinchona, Ashoka , Kurchi .

17. Underground Structures: Rhizomes, Roots, Bulbs and Tubers are the underground structures of the plant. They are swollen due to the storage of food material like carbohydrates and other chemicals. Examples: Ginger, Turmeric, Jatamansi .

18. Underground storage roots used as drugs are

19. Leaves: The shape, margin, base, apex and venation of leaves help in the identification of the drugs.

20. Flowers: These are the reproductive organs of a plant and possess different shapes, size and colour .

21. Fruits: Fruits arise from the ovary and contain seeds. They be globular, oblong or ellipsoidal in shape.

22. Seeds: Seeds are developed form the ovules in the carples of the flowers. They are characterized by the hilum-Nox vomica etc.

23. (b) Study of Sensory Characters: Colour , Texture, Odour and Taste are useful in the evaluation of drugs. Colour Odour Taste Texture

24. Colour : Some drugs are green in colour when dried in shade. But they become pale and bleached when dried in sunlight.

25. Odour : The odour of the drug may be either distinct or indistinct. The terms used for the drugs are aromatic, balsamic, spicy etc. Mentha , clove are some of the examples for the drugs which have a distinct odour .

26. Taste: The drugs may be evaluated by drugs taste also. The taste may be saline, sour, salty, sweet, bitter, alkaline etc. The substances without taste are regarded as tasteless. Examples: Ginger, Capsicum.

27. Texture: Sometimes drugs can be examinated by their consistency, texture and nature of fracture. Example: - Colocynth can be compressed easily since its parenchyma is loose.

28. 2. Microscopic or Anatomical Evaluation: This method allows a more detailed examination of a drug and it can be used to identify organized drugs by their known histological characters. Before examination through a microscope the material must be suitably prepared. This can be done by powdering, cutting thin sections(T.S or L.S) of the drug or preparing a macerate.

29. Microscope can also be used for a quantitative evaluation of drugs and adulterated powders. This is done by counting a specific histological feature such as: Stomatal Number Stomatal Index Vein-islet Number Palisade Ratio Quantitative Microscopy Refractive Index

30. Stomatal Number: The average number of stomata present per square millimeter of the epidermis is known as stomatal number. Stomatal number is relatively a constant for a particular species of same age and hence, it is taken into consideration as a diagnostic character for identification of a leaf drug. Example: Datura – 141 (upper epidermis)

31. Stomatal Index: It is the percentage proportion of the number of stomata to the total number of epidermal cells. Stomatal number varies considerably with the age of the leaf but stomatal index is relatively constant for a given species. Example: Atropa belladona – 20.0-23.0 (lower epidermis)

32. STOMATA A stoma (also stomate ; plural  stomata ) is a tiny opening or pore that is used for gas exchange.

33. Vein-islet Number: The term “vein-islet” is used for the minute area of photosynthetic tissue encircled by the ultimate divisions of the conducting strands. Vein-islet number is defined as the number of vein-islets per sq.mm. of leaf surface. It is constant for a given species of the plant. It is irrespective with the age factor. Example: Cassia angustifolia-senna (26).

34. Palisade ratio: It represents the average number of palisade cells present within one epidermal cell, using four continuous epidermal cells for the count. It is determined from powdered drugs with the help of camera lucida . Example: Atropa belladona – 06-10

35. Quantitative Microscopy: It is an important analytical technique for powdered drug, especially when chemical and other methods of evaluation of crude drug fail as accurate measure of quality. Why?? To determine the % purity of the crude drugs To detect the % of foreign matters (Starch) To check the limits of foreign matters Quantatity of Starch grains/Numbers The limit should not exceed 5% Example: Lycopodium spores from Lycopodium Clavatum - Spores are very characteristic in shape and appearance.

36. Important points to be remember Difference between Starch grain and Lycopodium grain (Yellowish spores, Spheroidal , triangular, kidney shaped, uniform diameter- 25-33  microns) Used when chemical and other methods of evaluation fails. Mainly used for powdered drugs (Ginger, Turmeric, Leaves, barks, Gums/Resins. 1mg of lycopodium contains 94,000 spores. Definite shape and sizes of spores which can be counted easily. Uniform moisture content due to uniform weight Resistance to pressure.

37. Requirements Weighing balance Lycopodium powder Sample (Ginger, Turmeric, Glycerine: Mucilage: Water (2:1:2)-Suspending agent, for enlargement of the specimen. Ginger starch grains Lycopodium spores

38. Microscopic view: Lycopodium spores & Starch grains

39. 3. Physical Evaluation: Physical contents such as elasticity in fibers, viscosity of drugs containing gums , swelling factor for mucilage containing materials , froth number of saponin drugs, congealing point of volatile and fixed oils, melting and boiling points and water contents are some important parameters used in the evaluation of drugs. Ultraviolet light is also used for determine the fluorescence of extracts of some drugs.

40. Physical constants are extensively applied to the active principles of drugs, such as alkaloids, volatile oils, fixed oils etc. A few of them are: - Moisture Content Viscosity Melting point Optical Ratation Refractive Index Ash Content Extractive values Volatile oil Content Rf Values

41. Moisture Content: Presence of moisture in a crude drug can lead to its deterioration due to either activation of certain enzymes or growth of microbes. Moisture content can be determined by heating the drug at 150⁰C in an oven to a constant weight and calculating the loss of weight.

42. Viscosity: Viscosity of a liquid is constant at a given temperature and is an index of its composition. Hence, it is used as a means of standardizing liquid drugs. Example: Liquid paraffin – less than 64 centistokes.

43. Melting Point: It is one of the parameters to judge the purity of crude drugs containing lipids as constituents. They may of animal or plant origin and contain fixed oils, fats and waxes. The purity of the following crude drugs can be ascertained by determining their melting points in the range shown against each of them. Example: Coca butter (30⁰ - 33⁰C)

44. Solubility: The presence of adulterant in the crude drug could be indicated by solubility studies.

45. Optical Rotation: Many substances of biological origin, having a chiral centre, can rotate the plane of polarized light either to right or to the left. The extent of rotation is expressed in degrees, plus(+) indicating rotation to the right and minus(-) indication rotation in the left. Such compound are optically active and hence called optical rotation.

46. Refractive Index: When a ray of light passes from one medium to another medium of different density, it is bent from its original path. Thus, the ration of velocity of light in vacuum to its velocity in the substance is said to the Refractive index of the second medium. It is measured by means of refractometer . Example: Arachis oil - 1.4678-1.4698

47. Ash value: The residue remaining after incineration of a known quantity of the air dried crude drug, is known as the ash content of the drug. Ash simply represents the inorganic salts naturally occurring in drug or adhering to it or deliberately added to it as a form of adulteration. Example: Ashoka – 11.00 Ginger – 6.00

48. Extractive values: In crude drugs, sometimes the active chemical constitutes cannot be determined by normal procedures. In such cases, water, alcohol or ether soluble extractive values are determined for evaluation of such drugs. Extractive value= Example: Water soluble extracts like Aloe vera Alcohol soluble like Ginger

49. Volatile oil content: Efficiency of several drugs is due to their odorous principle (volatile oils). Such crude drugs are standardized on the basis of their volatile oil contents. Weighed quantity of the drug is boiled with water in a round bottomed flask fitted with Clevenger apparatus. The distillate collected is graduated into volatile oil. The amount thus obtained is recorded from the tube.

50. Rf Values: Thin layer chromatography(TLC), has become increasingly popular for both qualitative and quantitative evaluation of drugs. Rf values refers to the ration of distance travelled by the solute to the distance moved by the solvent on a thin layer adsorbent. Distance travelled by the compound(solute) Rf = Distance travelled by the solvent

51. 4. Chemical Evaluation: Determination of the active constituent in a drug by chemical tests is referred to as chemical evaluation. The following are various methods of chemical evaluation: Instrumental methods Chemical Constants Individual chemical tests Micro chemical tests

52. Instrumental methods: They make use of various instruments for evaluation like colorimetry , flourimetry spectrophotometry -IR,UV- Vissible , etc. Chemical constants tests: These are like acid value, iodine value and ester value, etc are used for the identification of fixed oils and fats.

53. Individual chemical tests: These are the tests which are used for identifying particular drugs. Examples: Halpher’s test for cotton seed oil- Cyclopropenoid material Molisch’s test for carbohydrate Fische’s test for honey Millon’s test for protein Microchemical tests: These are the tests which are carried on slides. Example: On addition of s trong KOH solution, Euginol in clove oil is precipitated as potassium euginate crystals .

54. Qualitative phytochemical constituents of hydromethanol (HMPB) and petroleum benzene extract of Microcos paniculata barks (PBMPB)

55. Hydromethanol (HMPB) and petroleum benzene extract of Microcos paniculata barks (PBMPB) Chhitkari Gota Ful -Bangladesh Potka Ful -Bengali

56. 5. Biological Evaluation It is employed when the drug cannot be evaluated satisfactorily by chemical and physical methods. In this method, the response produced by the test drug on a living system is compared with that of the stranded preparation. In-vitro/ In-Vivo (Bio-assay) Such an activity is represented in units as International Units (I.U).

57. Indication of Biological Evaluation: When the chemical nature of the drug is not known but is has an biological action. When chemical methods are not available. When the quantity of the drug is small and so it cannot be evaluated chemically. Drugs which have different chemical composition but same biological activity. Example: Cardiac glycosides are evaluated by this method on cats, frogs or pigeons.

58. Plethysmometer (Paw Edema )

59. Vernier Caliper

60. 6. Analytical evaluation Thin Layer Chromatography Column chromatography GC-MS ASSIGNMENT

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