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:
1. Identity: Is the herb the one it should be?
2. Purity: Are there contaminants, e.g., in the
form of other herbs which should not be
there?
3. 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.”

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

12. 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.

13. 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

15. Methods of drug evaluation

16. 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.

17. • 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

18. 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.

20. 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.

21. • Underground storage roots used as drugs are

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

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

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

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

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

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

28. 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.

29.  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.

30. 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.

31. 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.

32. • 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

33. 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)

34. 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)

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

37. 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).

39. • 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

40. 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.

41. 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.

42. 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

43. Microscopic view: Lycopodium spores
& Starch grains

46. 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.

47. • 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

48. 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.

49. 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.

50. 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)

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

52. 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.

53. 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

54.  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

56. 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

57. 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.

59. 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

60. 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

61. 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.

62.  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 strong KOH solution, Euginol
in clove oil is precipitated as potassium euginate
crystals.

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

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

65. 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).

66. 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.

74. Plethysmometer (Paw Edema)

75. Vernier Caliper

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

77. Thank you