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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

TABLE OF CONTENTS

Sr. No Title of Practical Page


Number
1 Friability test of tablets 3
1.a Hardness test of tablets 10
1.b Weight variation test of tablets 14
2 Disintegration test of tablets 20
2.b Disintegration test of enteric coated tablets 25
3 Dissolution test of tablets 30
4 Weight variation test of capsules 34
5 Disintegration test of capsules 39
6 Assay of capsules 42
7 UV spectrophotometric assay of tablets 46
8 Assay of pyodine 50
9 Leaker test of parenterals 54
9.a Sterility test of parenteral 56
10 Quality Control Tests for suppositories 59
11 Quality Control Tests for Syrups 64
12 Quality Control Tests for Elixirs 68
Glossary 71

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Practical No 1

To Perform Friability Test of Given Sample of Tablets

Apparatus

Roche Friabilator

Construction of Roche Friabilator

A. Revolving Drum

a) Internal diameter………………286mm (B.P)

b) Depth………………………….39mm (B.P)

c) Made of transparent synthetic polymer polished from inner side.

d) Have removable front cover from front side.

e) Curved projection which extended from middle of drum to its surface. This projection is used
for placing the tablets. f)

Speed of drum

25 revolutions per min for 4 min or 100 revolutions in 4 min (B.P)

Height of tablet fall is 130 mm (B.P).This drum is fixing with horizontal

axis. g) Speed Regulator

For regulation of speed of the revolving drum through motor

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Diagram

Test Sample

Sample of tablets to be tested

Procedure

1) Selection of tablets
 We take 20 tablets if the weight of each tablet is < 650mg.
 We take 10 tablets if the weight of each tablet is >650mg.
2) Dusting of Tablets
Place the tablet over sieve number 1000 and dust the tablets by
a) Air pressure

It provide more exact readings because the dusts and etc particles removed by dusting
process.

b) Soft brush

Accurately weigh each tablet individually and then place in drum.

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3) Drum Rotation

Rotate the drum 100 times with speed of 25 revolution/min.

4) Re-dusting

Rotate the drum and separate the tablets again for redusting, because in redusting the
loosely attach particles with tablets are removed after when shocked by the rotating drum. It
gives more accurate weight.

Result Interpretation

a) If some tablets are split broken or cracked then the sample for testing is rejected. If no tablets
are split broken or cracked then way all the tablets.

b) If weight loss is less than or equal to 1% then batch is passed.

c) If weight loss is greater than 1% then take twice more tablets and perform the friability test 2
times and calculate mean of all three performed tests.

d) If mean show value less than or equal to 1% weight loss then it is passed and if greater than
1% then it is rejected.

nd
(If in first test the weight loss is less than or equal to 1% then no need of performance for 2 and
rd
3 test)

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Observation & calculations

Sr. Weight of individual Sum of weight of all tablets Sum of weight of all
No tablet before rotation tablets after rotation

W (mg) W1 (mg) W2 (mg)

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Formula

%F = W1-W2 x 100/W1

Where

W1 = Initial weight before rotation (Sum of weight of all tablets before rotation)

W2 = Final weight after rotation (Sum of weight of all tablets after rotation)

Limit: - Not more than 1% is allowed

Result

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Viva voce

Q # 1: What is friability test and why it is done?

The phenomenon where by tablets surface is damaged or show any signs of lamination or
breakage when subject to mechanical shock (force from 1 side) and attrition (force from all 4
sides). The test gives measure of resistance of tablet against applied force or pressure.

Q # 2: How tablets are selected for friability test?

 We take 20 tablets if the weight of each tablet is < 650mg.


 We take 10 tablets if the weight of each tablet is >650mg.

Q # 3: Is there a need to perform friability test of coated tablets?

There is no need of performing friability test of coated tablets as these tablets are tightly
packed in addition a coating of a polymer or a film protects tablet from external pressure.

PBL

1. It has been reported from QC department of an industry that the friability of batch under
manufacturing has found to be 6%. What could be the possible reasons for this?
The reasons for higher value of friability could be
 Low concentration of binder in the formulation
 Improper selection of binder
 Improper placement of dies of tableting machine
 Improper hardness level set at the tableting machine
2. A pharmacist working in the quality control section of an industry is supposed to check
the friability of different types of tablets. Will there be any difference in specifications
from the uncoated or plane tablets?

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Yes the specifications will be different for chewable and effervescent tablets. For
hygroscopic tablets particular hygroscopic environment is required.

3. The friability of a batch of tablet is found to be 8%. The batch was rejected. Is it a right
decision? What will be the effects of higher friability on the batch?
The decision is not correct as friability is an unofficial test and batch cannot be rejected
on the basis of its results. The higher friability affects weight uniformity, content
uniformity, hardness of tablet and reduces customer’s appeal towards the tablet.

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Practical No 1.a

Hardness Test for Given Sample of Tablets

Apparatus

Monsanto hardness tester

Diagram

Requirements

Sample of tablets to be tested

Specifications

2
Normal tablets………………………………………..4-6 kg/cm

2
Film coated/ sugar coated tablets…………………….5-10 kg/cm

Procedure

Check the zero error in the equipment by comparing the fixed scale zero point with the
zero point of movable piston. Place the tablet vertically in the apparatus. Tight the screw slowly
such that pressure is applied on the tablet. Keep on revolving the screw until the tablet breaks.
By reading the scale on the apparatus, note the pressure at the point where tablet breaks. Repeat
the procedure for 9 more tablets.

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Observations

Note hardness of each tablet individually.

Sr. Initial reading on the scale Final reading on the scale Net pressure applied
No
2 2 2
kg/cm kg/cm kg/cm

Result

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Viva Voce

Q # 1: Why hardness test is performed?

Hardness test is used to measure strength of tablet sufficient enough to resist breaking of
tablets during handling, packing and shipping. Hardness test is usually correlated with
friability test.

Q # 2: Write down name of instrument used to check hardness.

Monsanto hardness tester, Strong Cobb tester, Pfizer tester, 3in1 type PTB 311E (it
measures hardness, thickness & diameter of same tablet)

Q # 3: What is the difference between hardness and friability test?

Hardness test gives information about how much force can be tolerated by single tablet
whereas friability is measure of abrasion of tablet due its lower hardness.

PBL

1. In quality control test report a batch of tablets is found to be too hard. How this
problem can have impact on bioavailability of tablet?
In case of too much hard tablets the disintegration of tablet is reduced this leads to
delayed/reduced bioavailability.
2. The head of quality control department asked the QC analyst to give the hardness
test results in different units and also interconvert them. Is it possible?
Yes it is possible because different measuring equipment have different units. The units
2
of hardness are kg/cm Newton, strong Cobb and kilo pond
9.807N= 1kg by using this equation values can be converted.
3. The QC analyst reported about a batch of effervescent tablets that the batch is not up to
2
the mark as the hardness value is 1 kg/cm which is below the range of plane tablets.
Is the statement correct?

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No the statement is not correct because hardness values for effervescent tablets are
different from plane tablets.

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Practical No 1.b

To Perform Weight Variation Test for Given Sample of Tablets

Apparatus

Weighing balance, Petri dish

Diagram

Requirements

Sample of tablets to be tested

Specifications

B.P recommends the following

Weight of tablet ± %age Deviation allowed

80mg or less 10

>80mg – 250mg 7.5

>250mg 5

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USP recommends the following

Weight of tablet ± %age Deviation allowed

130mg or less 10

>130mg – 342mg 7.5

>342mg 5

Procedure

Take 20 tablets at random, weigh them individually and calculate the average weight.

Determine the weight variation for each tablet with the help of given formula.

Individual weight - Average weight x 100 /Average weight

Result Interpretation

A) Not more than 2 individual weights of tablet deviate from average weight by more than given
%age deviation.

B) None of tablets individual weight deviation by more than twice of the given % deviation.

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Observations & Calculations

Sr. No Individual weight of tablet Average weight %deviation= Individual weight -


Average weight x 100 /Average
weight

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Result

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Viva voce:

Q # 1: Maximum how many tablets can deviate from average

weight? 2 tablets can deviate from average weight.

Q # 2: Which type of weighing balance is used in weight variation test?

Analytical weighing balance

Q # 3: What is the allowed limit for weight variation?

Weight of tablet ± %age Deviation allowed

80mg or less 10

>80mg – 250mg 7.5

>250mg 5

PBL

1. During QC testing of a batch of tablets it was reported that weight variation up to


12% was observed in 8 tablets. What could be the reason?
The weight variation could be due to formulation error i.e. lack of flow promoting
agent, extra moisture content reducing flow and excessive binder leading to slower flow.
It could be due to process error i.e. variation in the size of punches of tableting machine,
friction in the hopper.

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2. In a hospital it was found that after administration of sedative in some patients toxic
effects were observed and in some sub-therapeutic effects were observed. The tablets
were not expired. What could be reason in your opinion?
It could be the result of weight variation leading to change in dose of API.
3. In production unit of an industry during regular maintenance of tableting machine it
was found that the dies of machine have be deformed. How it can affect the tableting?
The deformed dies can cause abrasion, breakage, change in shape and weight variation in
tablet.

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Practical No 2

To Perform Disintegration Test for Given Sample of Tablets

Apparatus

Disintegration test apparatus, beaker

Diagram

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Requirements

Sample of tablets to be tested

Specifications

British Pharmacopoeia

Tablet type Time limit and conditions

Uncoated <15 min

Coated

Film coated <30 min

Sugar coated <60 min

Enteric coated >120 min in 0.1M HCl then <60 min at pH 5.8

Effervescent < 5 min in 200ml water at 20˚C

Soluble < 3 min

Dispersible < 3 min 2 tablets in 100ml water

USP

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Tablet type Time limit and conditions

Uncoated < monograph time

Plain coated < monograph time

Enteric coated Intact for 60 min in simulated gastric fluid then


disintegrate in simulated intestinal fluid
<monograph time

Buccal < 4 hours

Sublingual < monograph time

Procedure

Introduce the tab/cap into each glass tube unless otherwise started in individual monograph.
Add perforated disc to each glass tube if described in its monographs. Usually disc is recommended
for the tabs having weight less than 200mg of floating tablets. Suspend the assembly into the beaker
containing liquid medium (water/simulated gastric fluid/simulated intestinal fluid) such that tablet
remains 2.5cm below the surface of the liquid on their upward movement and descent not closer than
2.5cm from the bottom of beaker, maintain at specific temp 37°C±1. Operate the apparatus for
specific time so that basket assembly moves up and down through a distance of 5-6cm at a frequency
of 28-32 cycles/min. There is different time for film coated tablets or sustain release tablets. Remove
the assembly from liquid medium after prescribed time.

Result Interpretation

B.P

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Observe the tabs/caps. If all six capsules have been disintegrated properly. Then our batch is
passed. If any one of cap/tab doesn’t disintegrate in prescribed time then batch is rejected.

U.S.P

If all the 6tablets disintegrate properly in prescribed time under prescribed experimental
conditions then batch is passed.

If one or two tab fails to disintegrate properly within prescribed time then repeat the test
with 12 more tablets and if not fewer than 16 tab/cap out of 18 tablets disintegrate properly then
our batch is passed.

Observations

Tablet type Disintegration time Inference

(min)

Uncoated

Film coated

Effervescent

Soluble

Dispersible

Sublingual

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Result

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Practical No 2.b

To Perform Disintegration Test for Enteric Coated Tablets

Apparatus

Disintegration test apparatus, beaker

Requirements

Tablets to be tested

Procedure

1. Stage 1
 Prepare 0.1M HCl one liter and one liter phosphate buffer of pH 6.8.
 Introduce one tablet into each glass tube.
 Add 0.1 M HCl in beaker.
 Maintain temperature of medium and suspend the assembly for 120 minutes.
 Operate it for 120 minutes.
 Then remove the assembly and observe it.

Note: No tablet should signs of crack that allows escape of contents of tablet.

2. Stage 2:
 Now replace the medium with mixed phosphate buffer of pH 6.8.
 Add a disc to each tube.
 Maintain the temperature of medium and suspend the assembly.
 Operate the apparatus for 60 minutes.
 Remove the assembly from beaker and observe it.

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Result interpretation

 Observe the tablets. If all 6 tablets have been disintegrated properly, than our batch is
passed.
 If any one of the tablets does not disintegrate in prescribed time, batch is rejected or failed.

Disintegration test for enteric coated tablets having external sugar coating

 Place one tablet into each glass tube. Add simulated gastric fluid and maintain
temperature at 37°c±2 in beaker. Suspend assembly into beaker and operate for one hour.
Remove assembly from liquid medium and observe it.

Note:
Tablets should show no signs of crack.

 Now replace liquid medium with simulated intestinal fluid and maintain at 37°c±2.
 Operate the apparatus for prescribed time. Lift the beaker and observe it.

Difference between stages of disintegration test and enteric coated tablets:

Operation Medium Disc

Stage 1 0.1 M HCl solution (120 min) No disc added

Stage 2 Mixed phosphate buffer (60 min) Disc added

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Observations

Tablet type Medium Disintegration time Inference

(min)

Result

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Viva voce

Q # 1: What are the applications of disintegration test?

 Disintegration test is a simple test which helps the formulator in the pre formulation stage.
 It helps in optimization of manufacturing variables such as compression force and dwell
time.
 The test is also simple in process, controlled tool to ensure uniformity from batch to batch
and among different tablets. It is also an important test in the quality control of tablets as
well as hard gelatin capsules.

Q # 2: Write down advantages & disadvantages of disintegration test.

Advantages:

 This test is simple in concept and in practice.


 It is very useful in pre-formulation, optimization and quality control.

Disadvantages:

 Disintegration test cannot be relied upon for assurance of bioavailability.

Q # 3: write down medium used in disintegration test of enteric coated tablets?

0.1M HCl solution, Mixed phosphate buffer

PBL

1. A new product has been designed and it is claimed that its onset of action is shorter than
the brand available in market. What lab tests should be conducted to check the claim? For
checking the claim perform dissolution test on the sample of new product that ia
designed.
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2. In case of sustained release tablets will there be any difference in disintegration test?
There is no change in case of sustained release tablets.
3. For a drug product it was claimed that onset time is one hour but it was observed that
onset time is three hours. What could be the possible reasons?
It could be due to improper disintegration & dissolution.

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Practical No 3

To Perform Dissolution Test for Tablets

Apparatus

 Volumetric flask
 Beakers
 Stirrer
 Weighing balance
 Pipette
 Dissolution test apparatus (rotating paddle apparatus)

Requirements

Sample of tablets to be tested

Chemicals

 Monobasic potassium phosphate


 NaOH
 Distilled water

USP dissolution apparatus

The paddle apparatus (Apparatus II) consists of a special, coated paddle that
minimizes turbulence due to stirring. The paddle is attached vertically to a variable-speed motor that
rotates at a controlled speed. The tablet or capsule is placed into the round-bottom dissolution flask,
which minimizes turbulence of the dissolution medium. The apparatus is housed in a constant-
temperature water hall maintained at 37°C, similar to the rotating-basket method. The position and
alignment of the paddle are specified in the USP. The paddle method is very sensitive to tilting.
Improper alignment may drastically affect the dissolution results with some drug products. The same
set of dissolution calibration standards is used to check the equipment before tests are run. The most
common operating speed for Apparatus II are 50 rpm for

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solid oral dosage forms and 25 rpm for suspensions. Apparatus II is generally preferred for
tablets. A sinker, such as a few turns of platinum wire, may be used to prevent a capsule or tablet
from floating. A sinker may also be used for film coated tablets that stick to the vessel walls or
help position the tablet or capsule under the paddle. The sinker should not alter the dissolution
characteristics of the dosage form.

Diagram

Procedure

Preparation of phosphate buffer (5.8):

Mix 3.6 ml of 0.2 M NaOH solution and 50 ml of 0.2 M KH 2PO4 solution and make up
the volume up to 200 ml with distilled water.

Place 900 ml of phosphate buffer of pH 5.8 in the vessel of dissolution apparatus.


Assemble the apparatus and equilibrate the dissolution medium to 37 ± 0.5°C and remove the
thermometer. Place one dosage unit in the apparatus taking care to exclude the air bubbles from
the surface of the dosage unit. And immediately operate the apparatus at 50 rpm.

Within the time interval specified (30 minutes for acetaminophen), withdraw a specimen
from a zone midway between the surface of dissolution medium and the top of the blade, but not
less than 1 cm from the vessel wall.

Medium:

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900 ml of phosphate buffer of pH 5.8

Speed:

Rotate at 50 rpm

Time:

30 minutes for acetaminophen

Add 1 tablet of acetaminophen in dissolution medium and operate the apparatus for 30
minutes. After 30 minutes take the sample from dissolution medium, make suitable dilutions and
find its absorbance at 243 nm. Solution must be filtered before taking absorption.

Note:

Not less than 80 % of the labeled amount should dissolve in 30 minutes.

Observations

Tablet type Medium Sample time Absorbance Inference

(min)

Result:

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Viva voce

Q # 1: What are different types of dissolution apparatus?

USP-I, II, III are different dissolution apparatus used in dissolution test.

Q # 2: What are different dissolution medium used in dissolution test?

Simulated gastric fluid, simulated intestinal fluid, water, 0.1M HCl

Q # 3: What is the limit of dissolution time for tablets?

It different for different types of tablets as per mentioned in monograph

PBL

1. For registration of a new drug product or an alternative product what QC tests are required?
Hardness, disintegration, dissolution and in vivo testing for bioavailability testing
2. For having complete dissolution profile of a product which studies are required?
Both in vivo and ex vivo studies should be conducted for complete dissolution profile.
3. A study reported that a particular product has lower dissolution profile. What are the
factors needed to be assessed for improving this?
Both formulation and process factors should be addressed for the assessment of ratio of
disintegrating agent and binder and compaction pressure which is applied while
manufacturing which increases hardness.

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Practical No 4

To Perform Weight Variation Test of Given Sample of Capsules

Apparatus

Weighing balance, Petri dish

Diagram

Requirements

Capsules 20

Specifications

Weight of Capsules ± %age Deviation Allowed

Less than 300mg 10

Greater than 300mg 7.5

Procedure

For hard Capsules

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Take 20 capsules randomly. Weigh an intact capsule (Active ingredient shell). Open the capsule
without losing any part of shell. Remove capsule content as possible. Weigh the shell. Calculate
the weight of contents by following formula.

Weight of contents = Weight of intact capsule – weight of shell

Repeat the same procedure for remaining 19 capsules.

For soft capsules

Take 20 capsules randomly. Weigh an intact capsule. Open or cut the capsule without losing any
part of shell. Remove the capsules content as possible. Wash the capsule with ether or other
suitable solvent and allowed to stand with no more odor of solvent is perceptible. Weigh the
shell. Calculate the weight of content by following formula.

Weight of content = Weight of intact capsule – weight of shell

Repeat the procedure for remaining 19 capsules.

Formula:

% weight variation = Individual weight – Average weight x 100/Average weight

Result Interpretation

Not more than 2 individual weights of capsules deviate from average weight by more than given
% deviation.

None of capsule individual weight deviates by more than twice of the given % deviation.

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Observations & Calculations

Sr. Weight of intact Weight of Content Average % deviation=Individual


No capsule shell weight weight weight – Average weight x
100/Average weight
(mg) (mg) (mg) (mg)

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Result

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Viva voce

Q # 1: Why not we separately weigh contents instead of weighing capsule shell?

Some amount of contents is wasted during emptying the capsule shell which reduces
accuracy of weight of content so it is not used for the purpose.

Q # 2: Why we wash the soft capsule?

Soft capsules are washed with ethanol or ether in order to completely remove the contents
from the shell

Q # 3: What is the sample size used for weight variation test of capsules?

Twenty capsules are used.

PBL

1. What can be possible draw backs if a batch of capsules is found to be highly variable in
weight?
It can lead to over dose or sub-therapeutic dose of API and can be lethal as well if API
has narrow therapeutic window
2. Is there any difference in weight variation testing of capsules & tablets?
The difference lies in the procedure. Tablets are weighed directly whereas in case of
capsules capsule shells are emptied and weight of content is measured indirectly.
3. What can be possible hazard for a batch of capsules which does not clear weight variation
test?
The batch will be rejected because it can cause deaths in case of toxic doses.

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Practical No 5

Disintegration Test for Hard Gelatin Capsule

Apparatus

Disintegration test apparatus, beaker

Requirements

Capsules to be tested

Procedure

 Introduce capsule in each glass tube unless otherwise stated in the individual monograph.
 Suspend the assembly in to the beaker containing liquid medium. Maintain at specific
temperature 37°c.
 Operate the apparatus for specific time. There are different times for different times for
different capsules mentioned in the monograph.
 Remove the assembly from liquid medium after prescribed team.

Result interpretation

B.P

Observe the capsules. If all six capsules have disintegrated properly, then our batch has
passed. If any one of the capsule does not disintegrate in prescribed time then , then batch
is rejected.

USP
If all 6 capsules disintegrate properly in prescribed time under prescribed experimental
conditions, then batch is passed. if 1 or 2 capsules is failed to disintegrate properly within
prescribed time, then repeat the test with 12 more tablets or capsules. And id not fewer
than 16 capsules/tablets out of 18 disintegrate properly, then our batch is passed.

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Observation

Sr. No Capsule type Disintegration time Inference

min

Result

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Viva Voce

Q # 1: What are the applications of disintegration test?

It gives an idea about onset of action and bioavailability.

Q # 2: What are the advantages & disadvantages of disintegration?

Disintegration is beneficial after administration as it is important for dissolution whereas

Disintegration before administration causes loss of API, patient compliance and


uniformity of dose.

Q # 3: Is there any difference in disintegration of soft and hard gelatin

capsules? There is no significant difference.

PBL

1. What can be possible draw backs if a batch of capsules is found to be highly variable in
weight?
It will lead to loss of uniformity of dose leading to increased risk of side effects.
2. Is there any difference in disintegration testing of capsules & tablets?
The difference lies in procedure i.e. a disk is placed on the capsules so that they may not
float during procedure
3. What can be possible hazard for a batch of capsules which does not clears disintegration
test?
It means the API will have decreased bioavailability leading to sub-therapeutic effects.

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Practical No 6

Assay of Capsules

Apparatus

 Weighing balance
 Volumetric flask
 Pipette
 Sucker
 Stirrer
 Burette
 Titration flask

Requirements

 Potassium iodide
 Iodine
 HCl
 NaOH
 Sodium thiosulphate
 Sodium carbonate
 Distilled water

Test sample

Cephradine capsules

Procedure

Preparation of 0.1 N iodine solution

Dissolve 10 g of potassium iodide in 6.5 g of iodine to make solution up to 250 ml with


distilled water.

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Take a valosef capsule and weigh it. Take out powder from capsule and note weight of
powder or alternatively weigh empty capsule shell. Find weight of powder by subtracting that from
whole capsule. Determine the amount of powder containing 25 mg of cephradine and dissolve it in
25 ml of distilled water. Then add 40 ml of 0.1 N NaOH solution and place it in dark for 15 minutes.
Then add 50 ml of 1 N HCl solution and 20 ml of 0.1 N iodine solution in above solution. Again
place it in dark for 15 minutes. Now titrate the solution against 0.1 N sodium thiosulphate solution.
End point will be colorless solution. Prepare the blank solution by mixing all chemicals in same
manner except adding cephradine and titrate it against sodium thiosulphate.

Observation & calculations

Sr. Volume used of Volume used of V1-V2= 5.2mL Inference


No sodium thiosulphate sodium thiosulphate 100%
in titration with in titration with
reaction mixture blank

V1 V2

Result:

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Viva voce

Q # 1: What is end point for titration?

End point of titration shows completion of reaction. It could be shown by appearance or


disappearance of color.

Q # 2: Write down formula to calculate %age purity.

Actual yield/theoretical yield * 100

Q # 3: Define titration.

Titration is a technique where a solution of known concentration is used to determine the


concentration of an unknown solution. Typically, the titrant (the know solution) is added
from a burette to a known quantity of the analyte (the unknown solution) until the
reaction is complete.

PBL

1. An 18 year old boy was brought to emergency department as his thumb nail was removed
in an injury. What should be medication given to him and why?
The wound should be cleared spirit swab and bandage should be done by applying
pyodine to swab to prevent infection
2. In field of quality control the term assay is used very commonly. What is its purpose and
what are ways to perform it?
Assay is basically a technique used to assess purity of a substance and its activity. It can
be done by Titration, Spectrophotometric analysis or bioassay can be conducted.
3. In a study it was reported that antibiotic resistance is increasing day by day. How this can
be prevented?

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st
It can be prevented by adopting the rational prescribing practice and start with the 1
generation antibiotics and don’t switch rapidly.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Practical No 7

UV Spectrophotometric Assay of Diclofenac Sodium

Apparatus

 UV visible double beam spectrophotometer

 Sonicator

 Volumetric cylinder

 Volumetric flask

 Mortar and pestle

 Weighing balance
Chemicals

 Diclofenac Sodium Standard

 Four different brand tablets of Diclofenac Sodium

 Distilled water

Procedure

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Standard Stock solution: - Accurately weigh 10 mg of diclofenac sodium standard


and transfer it to a volumetric flask and add sufficient water to produce 100 ml.

Sample Preparation: - Weigh Twenty tablets of four different brands of diclofenac sodium
each (labeled to contain diclofenac sodium 50mg per tablet) from the marketed sample and
crush uniformly with the help of a mortar and pestle. Calculate the average weighed sample
powder equivalent to 10 mg of diclofenac sodium and transfer into a volumetric flask
containing 10mL water. Sonicate the solutions for about 5 min and then add 100 ml water.

Procedure:- After preparation of standard and tablet solutions, (strength of solution 100
parts/million 100 ml ), check the absorbance of the sample preparation and standard
preparation in 1cm cell at the wavelength of maximum absorbance at about 340 nm, using
a spectrophotometer, using the blank solution. Then calculate the quantity in mg, of
diclofenac sodium per tablet and percentage assay of Diclofenac Sodium of each brand
and finally make a comparative analysis.

Observation & calculation

Experiment Observation Inference

Result

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Viva voce

Q # 1: What is the wavelength range associated with UV


spectroscopy? 200-400nm
Q # 2: Define Beer’s Law.
The absorption of light by a substance in a solution can be described
mathematically by the Beer-Lambert Law: 

A = ebc where

A = absorption at a given wavelength of light, e = molar absorptivity, unique to each


molecule and varying with wavelength, b = the path length through the solution that the
light has to travel,
Q # 3: Name the brands of Diclofenac sodium used for this practical.
Eufenac, Dicloran, Artifen

PBL
1. UV spectroscopy is an effective method to conduct assay of chemicals.
Draw the labeled diagram of a UV spectrophotometer.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

2. What is the difference between ‘identification test’ and ‘assay’?


Identification tests are intended to ensure the identity of an analyte in a sample. This is
normally achieved by comparison of a property of the sample (e.g., spectrum,
chromatographic behavior, chemical reactivity, etc) to that of a reference standard.
Assay procedures are intended to measure the analyte present in a given sample. In the
context of this document, the assay represents a quantitative measurement of the major
component(s) in the drug substance. For the drug product, similar validation
characteristics also apply when assaying for the active or other selected component(s).

3. What is the purpose of conducting an assay?


Assay procedures are intended to measure the analyte present in a given sample. In the
context of this document, the assay represents a quantitative measurement of the major
component(s) in the drug substance. For the drug product, similar validation
characteristics also apply when assaying for the active or other selected component(s).

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Practical No 8

Assay of Pyodine

Apparatus

 Beaker
 Burette
 Stirrer
 Funnel
 Volumetric flask
 Titration flask
 Weighing balance

Requirements

 HCl
 Sodium thiosulphate
 Phenolphthalein indicator

Procedure

First prepare sample solution by taking 20 ml of pyodine solution in 20 ml of 0.1 M HCl.


Then add sufficient amount of purified water to make final volume up to 100 ml. prepare 0.1 M
sodium thiosulphate solution. Titrate pyodine solution against sodium thiosulphate solution by
using phenolphthalein indicator, until solution becomes colorless.

Preparation of starch solution;

Take 0.5 g of starch in 100 ml of distilled water. Take 90 ml of boiling water and add
starch in it and boil for further 2 minutes.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Observation & calculation

Iodine test:

Add 1 ml of pyodine in 1 ml of starch solution. Formation of deep blue color indicates


presence of iodine.

Name of test Observation Inference

Calculation of amount taken

Calculation of actual amount

Sr. No Initial value of Sodium Final value of Sodium Volume used of


thiosulphate thiosulphate Sodium thiosulphate

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Factor:

1 ml of 0.1 M solution of sodium thiosulphate is equal to 12.69 mg of free iodine.

Calculate percentage purity by using:

Percentage purity = (actual amount/amount taken) x 100

Result

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Viva voce

Q # 1: What is end point for titration?

End point of titration shows completion of reaction. It could be shown by appearance or


disappearance of color.

Q # 2: How will you calculate actual amount present in reaction mixture?

Actual amount is obtained by multiplying the volume of titrant used with the factor value

Q # 3: Write down uses of pyodine.


It is used as antiseptic and is a part of first aid kit.

PBL

1. Pyodine is present in first aid boxes. Can you justify its presence over there?
Pyodine is an antiseptic which is applied on cuts and wounds that’s why it is present in
first aid box.
2. You are asked to check the end point or result of a chemical process. How will you do
that? End point of a chemical reaction is indicated by the indicator which could be
external or internal. Look for a color change, look for the solution to become color less.
Look for appearance of precipitates.
3. Usually it’s a common practice that for assessing quality of a product official and
unofficial tests are conducted. If the results of unofficial tests are not good will the batch
be rejected? No on the basis of results of unofficial tests batch is not rejected. It is
subjected for official tests.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Practical No 9

Leaker Test of Parenteral Formulations

Apparatus

 Beaker

Requirements

 Ampoules to be tested
 A colored dye

Diagram

Procedure

Take a beaker and place dye in it. Take ampoules which are transparent. Dip them in the
solution. Observe after some time. If any leak hole is present the colored solution will penetrate.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Observation

Name of test Observation Result

Result

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Practical No 9.a

Sterility Test of Parenteral Formulations

Apparatus

 Beaker
 Stirrer
 Petri plates
 Weighing balance
 Thermometer
 Bunsen burner
 Aluminium foil
 Cotton
 Gloves

Requirements

 Sample of formulation to be tested


 Agar media
 Laminar flow hood
 Incubator
 Autoclave

Diagram

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Procedure

Take beaker and stirrer. Wash them. Dry them. Switch on the UV lamp of laminar flow hood
15 minutes before conduction of practical and turn it off on completion of 15 minutes. Prepare agar
media by taking 2.8g agar and dissolve it in 100mL distilled water and heat it till 90ºc so that a
homogenous medium is prepared. Transfer the prepared medium into a flask. Place cotton plug on
the mouth of flask and wrap it with aluminum foil. Wrap the petri plates with aluminium foil. Place
the wrapped flask and plates in autoclave and sterilize them. After sterilization remove the wrapping
and transfer the agar medium in petri plates in such a way that two third of the plate is filled and
don’t fully remove the lid of plate for transferring the medium. Allow it to solidify. Label one petri
plate as control and other as experimental/test. Inoculate the test formulation by pour plate method
into the petri plate labeled as experimental/test. Place the control and test pates in incubator for 48
hours and after that observe for microbial growth and compare both plates.

Observation

Name of test Observation Result

Result

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Viva Voce

Q # 1: Define sterility.

Sterility means free from living germs.

Q # 2: What is leaker test?

Leak-testing glass ampules of injectable by means of vacuum- pressure treatment and


methylene blue dye solution

Q # 3: How will you prepare agar media?

Prepare agar media by taking 2.8g agar and dissolve it in 100mL distilled water and heat
it till 90ºc so that a homogenous medium is prepared.

PBL

1. For a patient who is 70y old what will be perfect route for administration of an oil base
injection?
It should be given IM because oil based injection causes irritation and severe pain when
given IV.
2. A patient has been on IV therapy for last two weeks. What will be the side effects?
The possible side effects are phlebitis, vein damage.
3. Different sterility levels are maintained for different products. What could be for
parenterals?
High grade sterility levels are maintained for parenteral product.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Practical No 10

Quality Control Tests for Suppositories

Apparatus

 Beaker
 Stirrer
 Burette
 Titration flask

Requirements

 Sample of suppositories to be tested


 0.1M NaOH solution
 Bromocresol purple

Procedure

Perform the quality control test by following procedure given below

1. Take the sample suppositories and observe for odor, color, shape and surface quality.
2. Perform weigh variation test of suppositories by taking 20 suppositories. Weigh them
and find out average weight. Then calculate percent variation individually. Not more
than two suppositories should deviate from average weight by 5% and none should
deviate by more than 10%.
3. Perform assay of glycerol suppositories. Official limit for the active contents is 95-
105% e.g. Glycerol Suppositories. Dissolve a number of suppositories equivalent to 8
grams of glycerol in 50 ml of water and add quantity sufficient to produce
250ml.Take 5ml of this solution and 150ml of water and 0.25ml of Bromocresol
purple solution and add 0.1M.NaOH to neutralize the blue color of indicator. Add 1.6
grams of sodium metaphenolate and allow to stand for 15 minutes and titrate with
0.1M NaOH to same blue color.

Percentage purity = (actual amount/amount taken) x 100

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Observations

Physical characteristics

Sr. No Name of parameter Observation Inference

Weight variation test

Sr. No Individual weight of Average weight %deviation= Individual weight -


suppository Average weight x 100 /Average
weight

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Assay

Calculation of amount taken

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Calculation of actual amount

Sr. No Initial value of NaOH Final value of NaOH Volume used of


NaOH

Factor

Each ml of 0.1M NaOH = 0.00921 grams of glycerol.

Percentage purity = (actual amount/amount taken) x 100

Result

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Viva voce

Q # 1: what are the conditions in which use of suppositories is recommended?

Suppositories are recommended for children in case of fever and constipation.

Q # 2: Write down names of suppositories available in market.

Glycerol suppositories, Paracetamol suppositories.

Q # 3: Is there any difference in bioavailability of a drug which is administered by rectal route?

The drug is more bioavailable as it bypass the first pass effect.

PBL

1. Suppository is not commonly used. What is the reason behind it?


Suppositories are not commonly used because of their limitation for a particular age
group as well as cultural issues
2. A child with broken skin and infection in throat reported to OPD. What will be choice of
dosage form and why?
Best route is oral route but if child is not able to swallow rectal route can be used.
3. How will you differentiate between liquefaction and melting?
Melting is complete transition of state from solid to liquid whereas in liquefaction the
transition is not complete its just softening of a solid mass.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Practical No 11

Quality Control Test for Syrups

Apparatus

 Beaker
 Stirrer
 Burette
 Titration flask

Equipment

 pH meter
 refractrometer

Requirements

 Sample of syrup to be tested


 0.1M NaOH solution
 Phenolphthalein

Procedure

Quality control tests are performed following the specific procedure.

1. First of all take sample in a transparent beaker and check its clarity.
2. Take 30 ml of sample in a beaker and check its pH by dipping electrode of pre -calibrated
pH meter into the sample and note the reading.
3. Check the refractive index of sample with the help of refractrometer.
4. Dilute it with the help of distilled water if it becomes miscible it means it is water soluble.
5. For assay of Lemon syrup mix 8 grams with 100ml of water and titrate with 0.1M NaOH
using phenolphthalein as an indicator.

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Observations

Sr. No Name of test Limitation Observation Inference

1 Consistency Clear

2 pH determination 6-7

3 Refractive index 1.4608 to 1.4630.

4 Solubility Water soluble

Assay of syrup

Calculation of amount taken

Calculation of actual amount

Sr. NoInitial value of NaOH Final value of NaOH Volume used of


NaOH

Factor

Each ml of 0.1M NaOH=0.007005 grams of C6H8O7.H2O

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Percentage purity = (actual amount/amount taken) x 100

Result

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Viva voce

Q # 1: Define syrups and give examples.

A liquid preparation of medicinal or flavoring substances in a concentrated aqueous solution of a


sugar, usually sucrose; other polyols, such as glycerin or sorbitol, may be present to retard
crystallization of sucrose or to increase the solubility of added ingredients. When the syrup
contains a medicinal substance, it is termed a medicated syrup; although a syrup tends (due to its
very high [approximately 85%] sucrose content) to resist mold or bacterial contamination, a syrup
may contain antimicrobial agents to prevent bacterial and mold growth.

Q # 2: Highlight the differences between USP & BP method of syrup formation.

The difference lies in concentration. USP syrup is 85% W/V whereas BP is 65% W/W

Q # 3: What is difference between suspension & syrup?

Suspension is a mixture with larger particle size of solvent which settles down when
allowed to stay whereas syrup is a homogenous mixture of substances completely dissolved in it

PBL

1. It is a common observation that syrups are packaged in amber color bottles. What is the
logic behind?
It is done in order to protect from light as it can initiate chemical reaction which may
change formulation.
2. Usually for antibiotics suspension are prepared at the time of use. Give reason.
It is done because antibiotics are more stable in solid form than the suspension form.
3. Water is a good medium for growth of microbes and it is a major part of syrup. Justify its
presence.
Water promotes microbial growth but at the same time it is best solvent for many APIs
that why it is used.

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Practical No 12

Quality Control Tests for Elixirs

Apparatus

 Beaker
 Stirrer

Equipment

 pH meter
 Refractrometer

Requirements

Sample of elixir to be tested

Procedure

Quality control tests are performed following the specific procedure.

1. First of all take sample in a transparent beaker and check its clarity.
2. Take 30 ml of sample in a beaker and check its pH by dipping electrode of pre -calibrated
pH meter into the sample and note the reading.
3. Check the refractive index of sample with the help of refractrometer.
4. Dilute it with the help of distilled water if it becomes miscible it means it is water soluble.

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Observations

Sr. Name of test Limitation Observation Inference


No

1 Consistency Clear

2 pH determination 6-7

3 Refractive index 1.4608 to


1.4630.

4 Solubility Water soluble

Result

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Viva voce

Q # 1: Define elixirs and give examples.

A clear, sweetened, hydroalcoholic liquid intended for oral use; elixirs contain flavoring
substances and are used either as vehicles or for the therapeutic effect of the active
medicinal agents. e.g. Bromophenaramine/ Pseudoephidrine elixir (Dimetapp)

Q # 2: What is the range of alcohol level in elixir?

The range of alcoholic content is 5-40%

Q # 3: Differentiate between syrup and elixir.

The difference lies in formulation. Elixir contains a higher proportion of alcohol whereas
syrups not necessarily contain alcohol.

PBL

1. Q.C and Q.A are the terms which are used simultaneously most of the time. Which one is
bigger in domain and contains other part and why?
QA is bigger domain and QC is a part of it because QC is the monitoring of set protocol
which is set by QA.
2. Elixirs are not commonly used. Why?
Elixirs are not used commonly because of the fact that they contain a higher ratio of
alcohol which can be dangerous if over dose occurs in addition to it there are social issues
regarding use of elixirs.
3. Elixir is a distinct dosage form what are its characteristics?
Elixirs are intended for oral use only. They have higher ratio of alcohol.

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Glossary
Accelerated testing: Studies designed to increase the rate of chemical degradation or physical
change of a drug substance or drug product by using exaggerated storage conditions as part of
the formal stability studies. Data from these studies, in addition to long term stability studies,
can be used to assess longer term chemical effects at non-accelerated conditions and to
evaluate the effect of short term excursions outside the label storage conditions such as might
occur during shipping. Results from accelerated testing studies are not always predictive of
physical changes.

Acceptance criteria: Numerical limits, ranges, or other suitable measures for acceptance of
the results of analytical procedures.

Accuracy: The accuracy of an analytical procedure expresses the closeness of agreement


between the value which is accepted either as a conventional true value or an accepted
reference value and the value found. This is sometimes termed trueness.

Active Ingredient: An Active Pharmaceutical Ingredient (API) is the chemical substance


contained in a pharmaceutical, which is responsible for its therapeutic effect.

Active Substance Master File (ASMF)/Drug Master File (DMF): is a document containing
complete information on an Active Pharmaceutical Ingredient (API) or finished drug dosage
form. It is known as European Drug Master File (EDMF) or Active Substance Master File
(ASMF) and US-Drug Master file (US-DMF) in Europe and United States respectively.

Aerobic Microorganism: A microorganism that utilizes oxygen as the final electron acceptor
during metabolism: a microorganism that will grow primarily in the presence of Oxygen.

Aerosol: Air suspension of solid or liquid particles having a volume median diameter of less
than 50 µm. The small size of the droplets or particles allows entry to the body via the
respiratory tract and readily contaminates clothing ,skin and eyes

Agglomeration: Adherence of particles in to a larger mass due to moisture, static charge or


chemical or mechanical binding.

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Aggregation: Accumulation or collection of particles in to larger units.

Amorphous: Solid substances that are not crystals.

Analgesic: A medication that reduces or eliminates pain.

Angle of repose: Angle of repose is the greatest angle form the horizontal that a heap of material
will remain stationary.

Analytical Procedure: The analytical procedure refers to the way of performing the analysis. It
should describe in detail the steps necessary to perform each analytical test. This may include but
is not limited to: the sample, the reference standard and the reagents preparations, use of the
apparatus, generation of the calibration curve, use of the formulae for the calculation, etc.

Anemometer: Anemometer is an instrument used to measure air flow velocity.

Antacid: An agent that counteracts or neutralizes acidity.

Antiemetics: Drugs used to treat nausea & Vomiting.

Anti-flatulent: Any agent that reduces intestinal gas.

Antineoplastics: Drugs used to treat cancer.

Antipyretic: A medication that reduces body temperature or pain.

Anaerobic Organism: A microorganism that does not utilize oxygen as the final electron
acceptor during metabolism: microorganism that will grow only in the absence of Oxygen.

Analyte: Substance for which analysis is being performed.

Annual Product Quality Review (APQR): APQR is overall review of the product
manufactured during the whole calendar year, for all the parameters including critical
parameters and trend of the batches.

ANDA: An application to market a generic drug in the USA. The application does not contain
extensive preclinical (pharmacology & toxicology) or clinical data. Instead an ANDA for a
typical tablet or capsule relies on therapeutic equivalence to the innovator product (or
reference listed product), together with an extensive CMC section.

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Aseptic Filling: The part of aseptic processing where a pre sterilized product is filled and / or
packed in to sterile containers and closed.

Aseptic Processing: Handling sterile materials in a controlled environment, in which the air
supply, facility, materials, equipment and personnel are regulated to control microbial and
particulate contamination to acceptable levels.

Aseptic Process Simulation: A means for establishing the capability of an aseptic process as
performed using a growth medium.

Note: Aseptic processing simulations are understood to be synonymous with media fills,
process simulations, simulated product fills, broth trials, broth fills etc.

Bar code: A way of labelling a product with a description and batch information using a
series of lines of various thickness that is read by a scanner.

Batch (or Lot): A specific quantity of material produced in a process or series of processes so
that it is expected to be homogeneous within specified limits. In the case of continuous
production, a batch may correspond to a defined fraction of the production. The batch size can
be defined either by a fixed quantity or by the amount produced in a fixed time interval.

Blow Fill Seal (BFS): Blow-fill-seal (BFS) technology is an automated process by which
containers are formed, filled, and sealed in a continuous operation. This manufacturing
technology includes economies in container closure processing and reduced human
intervention and is often used for filling and packaging ophthalmic, respiratory care products,
and, less frequently, injectable.

Bracketing: The design of a stability schedule such that only samples on the extremes of certain
design factors, e.g., strength, package size, are tested at all time points as in a full design. The
design assumes that the stability of any intermediate levels is represented by the stability of the
extremes tested. Where a range of strengths is to be tested, bracketing is applicable if the strengths
are identical or very closely related in composition (e.g., for a tablet range made with different
compression weights of a similar basic granulation, or a capsule range made by filling different
plug fill weights of the same basic composition into different size capsule shells).

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Bracketing can be applied to different container sizes or different fills in the same container
closure system.

Compounding: A process in which a bulk drug substance is combined with one or more
excipients and/or another bulk substance to produce a bulk product.

Compression: The process of reducing the bulk volume of a material by applying external
force.

Concurrent Validation: Validation carried out during routine production of products intended
for sale.

Contamination: The undesired introduction of impurities of a chemical or microbiological


nature, or of foreign matter, into or onto a raw material, intermediate, or API during
production, sampling, packaging or repackaging, storage or transport.

Critical Area: Area where sterilized products or containers/closures are exposed to the
environment (i.e aseptic preparation and filling).

Critical Process Parameter (CPP): A process parameter whose variability has an impact on
a critical quality attribute and therefore should be monitored or controlled to ensure the
process produces the desired quality.

Critical Quality Attribute (CQA): A physical, chemical, biological or microbiological


property or characteristic that should be within an appropriate limit, range, or distribution to
ensure the desired product quality.

D Value: Decimal reduction value (for biological indicators).The time in minutes required to
secure inactivation of 90% (one log) of the test organisms under stated exposure conditions.

Deduster: A piece of equipment that removes flashing and dust from solid dosage forms. It is
often combined with a metal detector and installed at the outlet of a tablet press or capsule filler.

Desiccant: A highly hygroscopic substance used to absorb moisture in bottles, vials, blisters
and other packing.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Design qualification (DQ): The documented verification that the proposed design of the
facilities, systems and equipment is suitable for the intended purpose.

Detection Limit: The detection limit of an individual analytical procedure is the lowest amount of
analyte in a sample which can be detected but not necessarily quantitated as an exact value.

Die: A circular machine tool with a central cavity in which powders or granular solids are
compacted in to tablet between the upper and lower punches of a tablet press.

DOP Test: Dioctyl Phthalate test is a test which used to check the HEPA filter integrity.

Enantiomeric Impurity: A compound with the same molecular formula as the drug substance
that differs in the spatial arrangement of atoms within the molecule and is a non-
superimposable mirror image.

Equipment Train: The sequence of equipment through which a product is produced or


processed.

Expiration date: The date placed on the container label of a drug product designating the
time prior to which a batch of the product is expected to remain within the approved shelf life
specification if stored under defined conditions, and after which it must not be used.

Factory Acceptance Test (FAT): Factory acceptance test is test conducted at the vendors
premises, to verify that the equipment/system operates according to the specifications.

Flashing: Small extrusions that appear around tablet periphery where the band meets the
cups. It usually flakes off during handling, dedusting or coating.

Friability: A measure of the resistance to abrasion and breakage of tablets during a


standardized test involving tumbling tablets in a rotating drum. Details of the equipment and
test protocol are found in all main pharmacopoeias. A limit of not more than 1% weight loss is
generally taken to be a satisfactory measure of friability.

Growth Promotion Test: Test performed to demonstrate the ability of the microbial media to
support microbial growth.

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PRACTICAL MANUAL OF QUALITY MANAGEMENT-I

Immediate (primary) pack: is that constituent of the packaging that is in direct contact with
the drug substance or drug product, and includes any appropriate label.

Impermeable containers: Containers that provide a permanent barrier to the passage of gases
or solvents, e.g., sealed labeling tubes for semi-solids, sealed glass ampoules for solutions.

Impurity: Any component of the new drug substance that is not the chemical entity defined
as the new drug substance.

Intermediate precision: Intermediate precision expresses within-laboratories variations:


different days, different analysts, different equipment, etc.

Intermediate testing: Studies conducted at 30°C/65% RH and designed to moderately


increase the rate of chemical degradation or physical changes for a drug substance or drug
product intended to be stored long term at 25°C.

Installation Qualification (IQ): The documented verification that the facilities, systems and
equipment, as installed or modified, comply with the approved design and the manufacturer’s
recommendations.

Investigation new drug application (INDA) – It is an application which is filled with FDA
to get approval for legally testing an experimental drug on human subjects in the USA.

Lamination: The presence of weak planes in a compressed tablet normal to the direction of
compaction. On subsequent handling or processing it is possible for the tablet to separate into
layers along these weak planes. Lamination may have the same causes as capping, or it may
also be a result of under lubrication of the tablet compression mix.

LD50: The dose of a material which results in 50% mortality in an animal test.

Leachable: Leachable are chemical entities, both organic and inorganic, that migrate from
components of a container closure system or device into a drug product over the course of its
shelf-life.

Lidstock: Material used to seal blisters to prevent or minimize moisture and/or gas permeation.

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Line Clearance: Line clearance includes a careful examination of the area and equipment
before batch to batch or product to product change over to avoid cross contamination.

Linearity: The linearity of an analytical procedure is its ability (within a given range) to
obtain test results which are directly proportional to the concentration (amount) of analyte in
the sample.

Marketing Pack: Marketing pack is the combination of immediate pack and other secondary
packaging such as a carton.

Modified Release: Dosage forms whose drug-release characteristics of time course and/or
location are chosen to accomplish therapeutic or convenience objectives not offered by
conventional dosage forms such as a solution or an immediate release dosage form. Modified
release solid oral dosage forms include both delayed and extended release drug products.

Mottling: ‘Mottling’ is the term used to describe an unequal distribution of colour on a tablet,
with light or dark spots standing out in an otherwise uniform surface.

Orally Disintegrating Tablet (ODI): An ODT is a dosage form designed to disintegrate or


dissolve quickly in the mouth without the need for water and without chewing. In general the
tablet should disintegrate within 30 seconds when tested using standard pharmacopoeial
disintegration apparatus, or another correlated disintegration test method.

Out of specification (OOS): Test result that does not comply with the pre-determined
acceptance criteria (i.e. for example, filed applications, drug master files, approved marketing
submissions, or official compendia or internal acceptance criteria).

Overage: Increased content of drug substance, usually due to loss of potency on storage.

Over Fill: Increased volume of drug product to account for loss during delivery.

Parametric Release: A sterility release system based upon effective control, monitoring,
documentation, and batch records review of a validated sterilization process cycle in lieu of
release procedures based upon end product sterility testing.

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Performance Qualification (PQ): The documented verification that the facilities, systems
and equipment, as connected together, can perform effectively and reproducibly, based on the
approved process method and product specification.

Pharmacopoeia: Pharmacopoeia is a book or encyclopedia of Drugs Standards, their


formulas, Methods for making medicinal preparations and other related information's which is
published under the jurisdiction of government body.

Picking: An imperfection caused by powders sticking to a punch surface during tableting.

Precision: The precision of an analytical procedure expresses the closeness of agreement


(degree of scatter) between a series of measurements obtained from multiple sampling of the
same homogeneous sample under the prescribed conditions. Precision may be considered at
three levels: repeatability, intermediate precision and reproducibility. Precision should be
investigated using homogeneous, authentic samples. However, if it is not possible to obtain a
homogeneous sample it may be investigated using artificially prepared samples or a sample
solution. The precision of an analytical procedure is usually expressed as the variance,
standard deviation or coefficient of variation of a series of measurements.

Primary batch: A batch of a drug substance or drug product used in a formal stability study,
from which stability data are submitted in a registration application for the purpose of
establishing a re-test period or shelf life, respectively. A primary batch of a drug substance
should be at least a pilot scale batch. For a drug product, two of the three batches should be at
least pilot scale batch, and the third batch can be smaller if it is representative with regard to
the critical manufacturing steps. However, a primary batch may be a production batch.

Probiotics: Probiotics are live microorganisms or microbial mixtures administered to improve


the patient's microbial balance, particularly the environment of the gastrointestinal tract and
the vagina. Probiotics have demonstrated an ability to prevent and treat some infections.
Probiotics can be bacteria,molds or yeast. Commonly used bacterial strains are Lactobacillus
& Bifidobacterium. Commonly used yeast strain is Saccharomyces boulardii.

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Process Analytical technology (PAT): A system for designing, analyzing and controlling
manufacturing through timely measurements critical quality and performance attributes of raw
and in-process materials and processes with the goal of ensuring final product quality.

Process-Related Impurities: Impurities that are derived from the manufacturing process.
They may be derived from cell substrates (e.g., host cell proteins, host cell DNA), cell culture
(e.g., inducers, antibiotics, or media components), or downstream processing (e.g., processing
reagents or column leachable).

Product-Related Impurities: Molecular variants of the desired product (e.g., precursors,


certain degradation products arising during manufacture and/or storage) which do not have
properties comparable to those of the desired product with respect to activity, efficacy, and
safety.

Process Validation: The documented evidence that the process, operated within established
parameters, can perform effectively and reproducibly to produce a medicinal product meeting
its predetermined specifications and quality attributes.

Production batch: A batch of a drug substance or drug product manufactured at production


scale by using production equipment in a production facility as specified in the application.

Quality Assurance (QA): The sum total of the organized arrangements made with the object
of ensuring that all APIs are of the quality required for their intended use and that quality
systems are maintained.

Quality System: The sum of all aspects of a system that implements quality policy and
ensures that quality objectives are met.

Quantitation Limit: The quantitation limit of an individual analytical procedure is the lowest
amount of analyte in a sample which can be quantitatively determined with suitable precision
and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of
compounds in sample matrices, and is used particularly for the determination of impurities
and/or degradation products.

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Quarantine: The status of materials isolated physically or by other effective means pending a
decision on their subsequent approval or rejection.

Reproducibility: Reproducibility expresses the precision between laboratories (collaborative


studies, usually applied to standardization of methodology).

Retrospective Validation: Validation of a process for a product which has been marketed
based upon accumulated manufacturing, testing and control batch data.

Revalidation: Repeated validation of an approved process to ensure continued compliance


with established requirements.

Risk Assessment: A systematic process of organizing information to support a risk decision to


be made within a risk management process. It consists of the identification of hazards and the
analysis and evaluation of risks associated with exposure to those hazards.

Risk Management: The systematic application of quality management policies, procedures,


and practices to the tasks of assessing, controlling, communicating, and reviewing risk

Robustness: The robustness of an analytical procedure is a measure of its capacity to remain


unaffected by small, but deliberate variations in method parameters and provides an indication
of its reliability during normal usage.

Saturated steam: Steam whose temperature, at any given pressure, corresponds to that of the
vaporization curve of water.

Specification: A list of tests, references to analytical procedures, and appropriate acceptance


criteria which are numerical limits, ranges, or other criteria for the tests described. It establishes
the set of criteria to which a drug substance or drug product should conform to be considered
acceptable for its intended use. “Conformance to specifications” means that the drug substance
and / or drug product, when tested according to the listed analytical procedures, will meet the
listed acceptance criteria. Specifications are critical quality standards that are proposed and
justified by the manufacturer and approved by regulatory authorities.

Standard operating procedure (SOP): An authorized written procedure, giving instructions for
performing operations, not necessarily specific to a given product or material, but of a more

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general nature, (e.g. equipment operation, maintenance and cleaning, validation, cleaning of
premises and environmental control, sampling and inspection). Certain SOPs may be used to
supplement product-specific master and batch production documentation.

Storage condition tolerances: The acceptable variations in temperature and relative humidity
of storage facilities for formal stability studies. The equipment should be capable of
controlling the storage condition within the ranges defined in this guideline. The actual
temperature and humidity (when controlled) should be monitored during stability storage.
Short term spikes due to opening of doors of the storage facility are accepted as unavoidable.
The effect of excursions due to equipment failure should be addressed, and reported if judged
to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours
should be described in the study report and their effect assessed.

Thermoforming: Thermoforming is a technique that involves heating sheets of PVC prior to


insertion into a blister machine. This is typically achieved by passing the sheets between upper
and lower heating plates. When a sheet enters a thermoforming blister machine, it is soft and
pliable and can be forced to take on the shape of a mold through the application of pressure. In
some cases, a mechanical stamp will be used in addition to the application of pressure,
particularly when the shape of the mold is difficult or complex.

Validation: A documented program that provides a high degree of assurance that a specific
process, method, or system will consistently produce a result meeting pre-determined
acceptance criteria.

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