Quality Control of Drug & Pharmaceuticals D. Pharm 1st yr

QUALITY CONTROL OF DRUG
PHARMACEUTICALS
3/24/2020 8:22 PM 1
Mr. Nandkishor Bavage
Latur College of Pharmacy, Hasegaon.
Maharashtra. India.
Maharashtra. India.

Definition:
Quality assurance:-
Quality assurance can be defined as "part
of quality management focused on providing confidence that quality
requirements will be fulfilled." The confidence provided by quality
assurance is twofold—internally to management and externally to
customers, government agencies, regulators, certifiers, and third
parties. An alternate definition is "all the planned and systematic
activities implemented within the quality system that can be
demonstrated to provide confidence that a product or service will
fulfill requirements for quality."
.
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• Quality Control:
• Quality control can be defined as "part
of quality management focused on
fulfilling quality requirements." While quality
assurance relates to how a process is
performed or how a product is made, quality
control is more the inspection aspect of
quality management. An alternate definition is
"the operational techniques and activities
used to fulfill requirements for quality."
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e.g.: If a disintegration time is not more than 15 min then,
if quality assurance technique are followed then the final
product will definitely give disintegration time below 15
min
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Functions of Quality Control
1. Analysis of Raw Materials
2. Analysis of in process products
3. Analysis of final dosage forms
4. Analysis of batch products .
5. Analysis of packaging materials
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Methods of Quality Control
Quality Control is to qualitative and quantitative analysis
Following are the various method for QC
1. Qualitative analysis:
i. Color
ii. Odor
iii. Taste
iv. Solubility
v. Identification tests
vi. Boiling point, Melting Point
vii. Limit Test
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2. Quantitative analysis:
I. Non instrumental Method:
i. Volumetric Method
ii. Gravimetric Method
i. VOLUMETRIC METHOD :
1) Acid-base titration
2) Redox titration
3) Precipitation titration
4) Complex metric titration.
ii. GRAVIMETRIC ANALYSIS
Estimation of Weight
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II. Instrumental Methods.
i. Electrochemical Technique:
1) Potentiometer
2) Conductometer
3) Colorimeter
4) Flurimeter.
ii. Spectroscopic Techniques:
1) Ultra visible spectrometer
2) Infra Red Spectrometer
3) Mass Spectrometer.
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iii. Chromatographic Techniques:
1) Column Chromatography
2) Paper Chromatography
3) Thin Layer Chromatography
4) HPLC
5) Gas Chromatography
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Importance of Quality Control
1. Quality control assures purity & Safety of medicinal
product.
2. It helps in preparing new drug application.
3. It helps to know the machines setting & modifications
in procedure of manufacturing.
4. It gives the desired quality of product after
manufacturing.
5. It also help to lower the cost of product.
6. It helps to maintain continuous production of quality
product.
7. It helps to locate & identify the defects in
manufacturing of the product.
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Precision: PRecise is Repeating. (or Repeatable)
Precision is defined as concordance of a series
of measurements of the same quantity
Accuracy: ACcurate is Correct. (or Close to real value)
Accuracy means closeness of an experimental
value with true value.
( Good precision is not necessarily accurate)
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Errors
Definition;
It is difference between measured value and
true value.
There are two types of errors.
1. Determinate errors (Systematic/Constant)
2. Indeterminate/Random/Accidental error
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I. Determinate Errors
i. These errors are determinable &
presumably can be either avoided or
corrected.
ii. They arise from causes such as
1. Personal errors
2. Method/Procedure
3. Instrumental
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1. Personal errors
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1. Personal errors:
Personal errors made by the individual
analyst.
e.g.
i. Poorly judged visual end points due to
Colorblindness or due to late reading of
end points.
ii. Mathematical errors in calculation.
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2. Method Errors
Errors of the method caused by incorrect
procedure.
eg:
i. Incorrect sampling,
ii. contamination of precipitates,
iii. impurities in reagents
iv. improper selection of indicators.
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3. Instrumental:
Instrumental or apparatus errors due to poor
construction or calibration.
eg:
i. Incorrect weights due to faulty weighing
balance.
ii. Uncalibrated or faulty glassware's like
Burettes & Pipettes.
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II. Indeterminate Errors (Random/Accidental error)
i. These errors are revealed by slight
variations in a series of measurements or
observations made by the same analyst
under identical conditions.
ii. These errors are difficult to detect.
iii. Evaluation of such errors require statistical
method, random distribution.
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Significant Figure
Def. Significant figure are the digits necessary to express the results of a measurement which
are consistant with the measured precision.
Zero are employed to donate the significant part of measurement.
Thus, zero within a number like 11.05 and 1540 are significant as they gives exact
quantity, while zero before decimal in figures, like 0.0234 only shows the magnitude of
other digit.
in case of units, the quantity 0.0056 gm, the zeros are significant number, but in the
quantity 0.0035 kg the zeros are even though significant, but that zero serve only to
locate decimal point and can be eliminated by using proper units i.e. 3.5 gm.
so in case of 0.0056 gm there are five significant number but in case of 0.0035 kg there
are two significant numbers.
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IMPURITIES
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IMPURITIES
Impurities:
It is the undesirable material which is not a part of
drug or medicinal substance.
That may be toxic or non- toxic.
Sources of Impurities:
1. Raw Material
2. Process used in Manufacture
3. Material of the plant
4. Inadequate storage
5. Adulteration
6. Particulate contamination
7. Microbial Contamination
8. Packing Errors
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Maharashtra. India.

IMPURITIES
Sources of Impurities:
1. Raw Material:
If the raw material contain impurities then the
final product will impure.
e.g.
i. Sodium ion are present as impurity in sodium chloride .
ii. Copper Sulphate prepared from Copper pyrites may contain traces of iron
then the impure Copper sulphate will form.
iii. Water is required for the number of experiments or process in industry But
if normal Tap water will used for that experiments then the final products
will be form in impure form because in tap water contain number of
impurities like Chloride, Calcium, Magnesium which contaminate the
products.
3
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2
4
/
2
0
2
0 22
Maharashtra. India.

IMPURITIES
2. Process used in the manufacture :
The process or method of manufacture may introduce
new impurities into the final product arising due to
contamination by reagents, catalysts and solvents
employed at various stages of the manufacturing
process.
Due to this some impurities comes into final product
during manufacturing processes. To avoid impurities
suitable manufacturing process should be adopted.
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Maharashtra. India.

3. Material of the plant:
The equipment or utensils used in the manufacturing
process are constructed out of metals like
Copper, Aluminum, Iron, Zinc, Nickel & Tin or
Stainless steel. Due to action of the solvents on the
material of the equipment or utensils, traces of the
metals are introduces as impurities in the compound.
Eg. Water pipe material in water
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Maharashtra. India.

4. Inadequate Storage:
Many chemical substances undergo changes
or decomposition due improper storage of
both raw materials and finished product.
e.g.
i. Due to careless storage of Ferrous sulphate
is slowly converted into insoluble ferric
oxide by air & moisture.
ii. Bismuth carbonate becomes blackened on
long exposure to sunlight.
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Maharashtra. India.

5. Adulteration:
The Cheap substances are added in pure
substances as substitute and therefore added
substances acts as an impurity in pure
substances.
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Maharashtra. India.

6. Particulate Contamination:
This type of impurities may get
incorporated at various stages of
manufacturing . It involves pieces of plastics,
threads in the products due to improper
cleaned equipments and also due to wear
and tear equipments.
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Maharashtra. India.

7. Microbial contamination:
Liquid or creams may be contaminated
due to bacteria , viruses and fungi from
atmosphere.
8. Packing Errors:
Impurities result also from packaging
methodology and materials used for packing
i.e., containers and closures . For moist drugs
hydrolysis of active ingredient happens and
impurities may occurs .
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TYPES OF IMPURITIES
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TYPES OF IMPURITIES
1. Toxic Impurities:
If impurity is present above the prescribed limit and
produces toxic effects on the body, it is called as toxic
impurities.
e.g. Lead , Arsenic impurities.
2. Harmless Impurities:
Some impurities are harmless but if present above the
prescribed limit , they lower active strength of
substances.
e.g. Impurities of sodium salt in potassium salt.
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Maharashtra. India.

TYPES OF IMPURITIES
3. Impurity affecting storage property:
Presence of moisture beyond the limit affects the
storage property of pharmaceuticals.
Eg. Presence of high water content in drug may
reduces flow property and affect the storage.
4. Impurity causing technical difficulties:
Impurity causes many technical problems during
manufacturing . Picking and sticking defects may
occurs in tablet manufacturing.
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TYPES OF IMPURITIES
5. Impurities affecting taste, odour and appearance of
the products .
Eg. Phenolic impurities present in sodium salicylate
alters its odour.
6. Impurities lower the shelf life of substances.
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Maharashtra. India.

LIMIT TEST
Def:
These are the qualitative test used to identify
and control the small amount of impurities
present in the pharmaceutical substances.
1. Limit test for Chloride
2. Limit Test for Sulphate
3. Limit test for Heavy metals
4. Limit Test for Iron
5. Limit test for Arsenic
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1. LIMIT TEST FOR CHLORIDE
Principle:
Limit test of chloride is based on the reaction of
soluble chloride with silver nitrate in presence of
dilute nitric acid to form silver chloride, which
appears as solid particles (Opalescence) in the
solution.
Reaction :
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Cl + AgNO3
AgCl + NO3
Dil. HNO3
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1. LIMIT TEST FOR CHLORIDE
Procedure :
Test Solution :
Weigh accurately substance + 10 ml of dilute HNO3 +
50 ml of water + 1ml of 1% AgNO3 solution.
Standards:
1ml of NaCl solution + 10 ml of dilute HNO3 +
50 ml of water + 1ml of 1% AgNO3 solution.
Stir both solution and keep a side for 10 min.
Observation :
If the opalescence produced in test solution is less than
standard solution , substances that passes the limit test for
chloride IP.
Reasons:
Nitric acid is added in the limit test of chloride to make solution acidic
and helps silver chloride precipitate to make solution turbid at the end
of process.
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Maharashtra. India.

2. LIMIT TEST FOR SULPHATE
Principle:
Limit test of sulphate is based on the reaction of soluble
sulphate with barium chloride in presence of dilute
hydrochloric acid to form barium sulphate which appears
as solid particles (turbidity) in the solution.
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BaSO4 + 2 ClSO4 + BaCl2
Dil HCl
Maharashtra. India.

Procedure:
Test Solution :
Weight of substance + 2 ml of Dil. HCl + 50 ml of water. + 5 ml
of BSR (Barium sulphate reagent )
BSR Composition: BaCl2 solution , Alcohol, Potassium
sulphate solution .
Standard Solution :
2.5 ml of H2SO4 + 2 ml of Dil. HCl + 50 ml of water. + 5 ml
of BSR . Stir both solution and keep a side for 10 min.
Observation :
Sulphate IP.
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Test sample Standard compound
Specific weight of compound is dissolved in water
or solution is prepared as directed in the
pharmacopoeia and transferred in Nessler cylinder
Take 1ml of 0.1089 % W/V solution of potassium
sulphate in Nessler cylinder
Add 2ml of dilute hydrochloric acid Add 2ml of dilute hydrochloric acid
Dilute to 45 ml in Nessler cylinder Dilute to 45 ml in Nessler cylinder
Add 5ml of barium sulphate reagent Add 5ml of barium sulphate reagent
Keep aside for 5 min Keep aside for 5 min
Observe the Turbidity Observe the Turbidity
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Procedure:
(Barium sulphate reagent contains barium chloride, sulphate free alcohol and small amount of
potassium sulphate.)
Observation:
The turbidity produce in sample solution should not be greater than standard solution.
If turbidity produces in sample solution is less than the standard solution, the sample
will pass the limit test of sulphate and vice versa.
Maharashtra. India.

Reasons:
Hydrochloric acid helps to make solution
acidic.
Potassium sulphate is used to increase the
sensitivity of the test by giving ionic
concentration in the reagent
Alcohol helps to prevent super saturation.
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Maharashtra. India.

3. LIMIT TEST FOR HEAVY METALS
Principle:
Heavy metals impurities reacts with H2S in presence of
acidic / alkaline medium to form brown ppt of metal sulphide.
Here acidic medium can be adjusted by acetic acid
while alkaline medium adjusted by NaOH.
Reaction :
M + H2S MS + 2H
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3. LIMIT TEST FOR HEAVY METALS
Procedure:
Test solution :
Weigh accurately solution and trasfer it in Nessler’s cylinder + Add
dilute acetic acid / ammonia to adjust pH between 3-4 + 35 ml of
water + 10 ml of H2S + dilute up to 50 ml with water.
Standard Solution :
Take 2 ml of lead sulphate solution + Add dilute acetic acid /
ammonia to adjust pH between 3-4 + 35 ml of water + 10 ml of H2S
+ dilute up to 50 ml with water. Stir both solution and keep a side for
10 min.
Observation :
Heavy Metals IP.
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4. LIMIT TEST FOR IRON
Principle:
Limit test of Iron is based on the reaction of iron in ammonical
solution with thioglycollic acid in presence of citric acid to form iron
thioglycolate which is pale pink to deep reddish purple in color.
Purple color develops only in alkaline medium, so iron free ammonia is
used, but ammonia solution forms precipitate with iron, so iron free
citric acid is added to prevent this precipitation of iron with ammonia.
Role of Thioglycolic acid-
Iron impurity may be present in trivalent ferric form or in the
divalent ferrous form. If it is in ferric form, thioglycolic acid convert
ferric form of impurity into ferrous form and then forms ferrous
thioglycolate complex.
Role of Citric acid:
It prevents the precipitation of iron in presence of ammonia
Role of Ammonia:
It maintains alkaline pH for the formation of stable purple colored
ferrous thioglycolate complex.
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2 Fe3+ + 2 SH•CH2•COOH 2 Fe2+
+ HOOC•CH2•S•S•CH2• COOH + 2 H+
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Fe2+ + 2 SH•CH2•COOH + 2 H+
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4. LIMIT TEST FOR IRON
Procedure:
Observation :
If the opalescence produced in test solution is less than standard
solution , substances that passes the limit test for iron IP.
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Maharashtra. India.

Limit Test for Arsenic
Principle:
• Arsenic is an undesirable and harmful impurity in medicinal
substances, and all Pharmacopoeias prescribe a limit test for it.
• The Pharmacopoeial method is based on the Gutzeit test.
• When the sample is dissolved in acid, the arsenic present in the
sample is converted to arsenic acid.
• The arsenic acid is reduced, by reducing agents (like potassium
iodide, stannated acid, etc.) to arsenious acid.
• The nascent hydrogen produced during the reaction, further
reduces arsenious acid to arsine (AsH3 gas), which reacts with
mercuric chloride paper, producing a yellow stain of mercuric
arsenide.
• The intensity of the stain is proportional to the amount of
arsenic present.
• A standard stain produced from a definite amount of arsenic, is
used for comparison
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• Principal with Reaction :
1) Limit test for arsenic is based on semi quantitative
determination of arsenic impurities in the test sample of
drug. The sample is dissolved in stannated acid, which
converts the arsenic impurities to arsenious acid or
arsenic acid depending upon valence state of arsenic
impurity present in the test sample.
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2) When acidic solution of sample treated is
with reducing agent(stannous chloride)
converts pentavalent arsenic acid into the
trivalent arsenious acid.
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3) The arsenious acid is then converted into
gaseous arsenious hydride (arsine gas) with
the help of nascent hydrogen (which is
produced by zinc and hydrochloric acid).
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4) Arsine gas is carried through the tube by
the steam of hydrogen and out through the
mercuric chloride paper. A reaction occurs
between arsine and mercuric chloride, which
produces mercuric arsenide of yellow colour
stain.
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5) The stain produced by test sample
compared with that of standard arsenic
solution.
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Procedure:
Test Solution :
Substance + 1 gm of KI + 10 mg of Stanated zinc . Shake the
bottle and keep aside for 40 min.
Standard Solution:
0.2 to 1 ml standard arsenic solution + 1 gm of KI + 10 mg of
Stanated zinc . Shake the bottle and keep aside for 40 min.
Observation :
If yellow stain obtained in test mercuric chloride paper is less
than standard stain , sample passes limit test for arsenic
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Guitzeit Test Apparatus
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Guitzeit Test Apparatus
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Construction:
1. It consist of a wide mouthed glass bottle of capacity 120 ml .
2. Glass tube having its length is 200 mm and internal diameter 6.5 mm is
passed through the rubber bungs.
3. Glass tube having 2 mm hole at the lower end of tube .
4. The end of tube should be above the liquid.
5. HgCl2 paper is sandwiched between two rubber bungs and fixed by clip.
6. Lead acetate cotton plug is inserted into the glass tube before
operation.
7. When reaction starts, arsine gas is formed which goes upward through
glass tube.
8. The impurities present in arsine gas are trapped by lead acetate cotton
plug.
9. The arsine gas passed through lead acetate cotton plug and react with
mercuric chloride paper to form yellow stain.
Maharashtra. India.

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