Quality Control Tests for Tablets, Capsules, Powders, Creams, Ointments

1. Presented By
Y.Divya
M.Pharmacy Ist Year I sem
Pharmaceutical analysis
SPMVV

2. o Introduction to Quality control
oTypes Of Solid & Semi Solid Dosage Forms
oQuality Control Tests For Capsules
oQuality Control Tests For Powders
oQuality Control Tests For Creams And Ointments
oConclusion
oReferences

3. Quality control: It is a small part of QA that is concerned with
sampling,
testing and
documentation during manufacturing and also
after completion of manufacturing.
Definition:
In general terms, Quality control refers to a set of steps taken
during manufacturing of a product to ensure that it meets the
requirements and that the product is reproducible.

4. Quality Control Tests For Capsules
oSolid unit dosage forms
oMedicinal agents and/or inert substances are enclosed in
a small shell of gelatin
oGelatin capsule shells may be hard or soft, depending
upon their composition.

5. The Quality control tests to be performed
for Capsules are:
Quality
Control
Test
Uniformity of
mass
Uniformity of
contents
Content of
active
ingredients
Uniformity Of
weight
Dissolution
Disintegration

6. 1.Uniformity Of Weight:
Weigh Intact Capsule
Open the capsule and
Remove the contents without losing any part of
shell
For soft capsules, contents are removed by
washing shell with ether or suitable solvent
Now weigh empty shell.
Difference in weights gives Weight of contents
Repeat procedure with 19 capsules.
Determine average weight

7. 2.CONTENT OF ACTIVE INGREDIENT
The amount of active ingredient is determined by the method described
in Assay
3. UNIFORMITY OF CONTENT
•Applicable to capsules that contain less than 10mg or less than 10 %
w/w of active ingredient.
•For capsules containing more than one active ingredient, the test has to
be carried out for each active ingredient.
•This test should be carried out only within the accepted limits of the
stated amount.
•The content of active ingredient is determined by taking each of 10
capsules randomly using method given in monograph or by any other
suitable analytical method of equivalent accuracy and precision.

8. 4.UNIFORMITY OF MASS
Weigh Intact
Capsule
Open the capsule
Remove the contents
without losing any
part of shell
Difference in weights
gives Weight of
contents
Now weigh
empty shell
For soft capsules,
contents are removed
by washing shell with
ether or suitable
solvent
Repeat procedure
with 19 capsules
Determine average
weight

9. 5.DISINTEGRATION TEST:
Repeat the test omitting the disc
preparation complies with the test if all the capsules tested disintegrate
NLT 16 of the total of 18 capsules tested disintegrated
If the capsules adhere to the disc or Fail to comply test
Assembly was removed from liquid
Pass the test if all of them are disintegrated
1 or 2 capsules fail to disintegrate, repeat
the test with 12 additional capsules
Introduce one capsule into each tube and,
add a disc if indicated.
Suspended it in beaker containing specified
liquid
operate the apparatus for the specified time.

10. Draw samples & perform analysis as directed in monograph
Lower the basket & Operate
Paddle: Allow capsule to sink to bottom of vessel
Basket: Place in dry basket at beginning of test
Place one capsule in apparatus
Assemble & warm to 36.5oC to 37.5oC
Place stated volume of dissolution medium in apparatus
6.DISSOLUTION TEST

11. Tests IP BP USP
Uniformity of
weight
90-110% NS NS
Content of active
ingredient
NS <10% NS
Uniformity of
content
85-115% 85-115% 85-115%
Uniformity of mass <10% <10% <10%
Disintegration test
Hard capsules <30min <30min <30min
Soft capsules <60min <60min <60min
Enteric capsules 3hrs NS NS
Gastro-resistant 3hrs NS NS
Quality Control Parameters For Capsules As per IP, BP USP

12. Quality Control Tests For Powders
Powders are subdivided solids which are classified according to the size of
their constituent particles which range from <1.25 micrometer to 1.7mm
Classification Of Powders:
1.Bulk powders
2.Divided powders
3.Dusting powders
4.Insufflations

13. Quality Control Tests To Be Performed Are:
•Particle size analysis
•Angle of repose
•Bulk density
•Tapped density
•Hausner’s ratio
•Flowability

14. 1.Particle Size Analysis:
The powders have been classified into:
As per vegetable & Animal origin:
Very Coarse(#8): All particles pass through sieve no.8 and not more than
20% through sieve no.20
Coarse (#20): all particles pass through sieve no.20 not more than 40%
through sieve no.60
Moderate(#40): All particles pass through sieve no.40 and not more than
40% through sieve no.60
Fine(#60): All particles pass sieve no.60 and not more than 40% through
sieve no.80
Very Fine: All particles pass through this sieve. There is no limits as to
greater fineness.

15. Powders of chemical drugs are classified as:
Coarse (#20): All particles pass through sieve no.20 not more than 40%
through sieve no.60
Moderate(#40): All particles pass through sieve no.40 and not more
than 40% through sieve no.80
Fine(#60): All particles pass sieve no.60 and not more than 40% through
sieve no.80

16. 2.Powder Flowability:
Powder flowability is the ability of powder to flow in a desired
manner in a specific piece of equipment.
Flow of powders may be:
•Free flowing
•Non-flowing or cohesive.
Flow Patterns:
•Funnel Flow
•Mass Flow

17. Measurement of Flow properties:
Flow
Properties
of Powder
Penetometry
Powder
Rheometer
Cohesive
index
Shear cell
method Flow
through
Orifice
Carr’s Index
& Hausner’s
ratio
Angle Of
Repose

18. Angle of Repose:
The internal angle between the surface of the pile and height of the
pile.
It depends upon:
•Density
•Surface area
•Shape of the particles
•The coefficient of
friction of material
Flow Property Angle of Repose (degrees)
Excellent 25–30
Good 31–35
Fair—aid not needed 36–40
Passable—may hang up 41–45
Poor—must agitate, vibrate 46–55
Very poor 56–65
Very, very poor >66

19. Carr’s Index & Hausner’s Ratio:
Both are determined by measuring bulk volume and tapped volume of
powder
Compressibility
Index (%) Flow Character Hausner Ratio
10 Excellent 1.00–1.11
11–15 Good 1.12–1.18
16–20 Fair 1.19–1.25
21–25 Passable 1.26–1.34
26–31 Poor 1.35–1.45
32–37 Very poor 1.46–1.59
>38 Very, very poor >1.60

20. Flow Through An Orifice:
•Useful only for free flowing powders.
Types Of flow Rate:
•Mass flow rate: Quantity of powder flow per minute.
•Volume flow rate: Time taken by the powder in a container to
drain out.

21. Shear Cell Method:
In the shear cell method, the force necessary to shear the powder bed by
moving the upper ring is determined.
Flow Factor Index Flowability
ff < 1 Non flowing
1 < ff < 2 Very Cohesive
2 < ff < 4 Cohesive
4 < ff < 10 Easy flowing
Ff > 10 Free Flowing

22. COHESION INDEX:
Determined by integrating the negative areas under force displacement
curve.
A low cohesion index is
associated with non-cohesive
free flowing powders

23. FT4 POWDER RHEOMETER:
The forces causing deformation of powders is measured here.
This gives measurement of:
•Flow energy
•Shear properties
•Bulk properties
Downward Test Mode:
Used to measure Basic Energy Flow(BEF)

24. Upward Test Mode:
Used to measure the Specific Energy(SE) which is flow energy per
gram of powder tested.

25. PENETROMETRY:
The pressure of penetration in pascal was used to estimate flow rate.
Particle size should be in the range of:
0.250-0.630 mm
Especially used for non-consolidated pharmaceutical powder
excipients:
•Sodium chloride
•Sodium citrate
•Boric acid
•Sorbitol

26. Quality Control Tests For Semisolid Dosage Forms
Semisolid dosage forms are products of semisolid
consistency and applied to skin or mucous membrane
for therapeutic or protective action or cosmetic
function
Types:
Ointments
Creams
Gels
Pastes
Poultices
Semisolid foams

27. Quality Control Tests For Creams & Ointments
Universal Tests
Description
Identification
Assay
Impurities
Specific Tests
PH
Apparent Viscosity
uniformity Of Dosage Unit
Water Content
Microbial Limit
Preservative Effect
Particle Size
Special Tests
Phase Separation
Uniformity in Container
In vitro Release Studies

28. 1.Universal Tests:
Description:
This includes visual examination to identify changes in color, separation,
crystallization etc., in the final appearance of the product.
The description should specify the content or label claim of the product.
2.Identification:
Quantitative identification of active ingredients in the finished dosage
form.
Methods:
•IR
•Raman spectroscopy
•Chromatography

29. 3.ASSAY:
The quantity of drug present in unit weight or volume of ointment or
cream is determined by:
•Spectrophotometric method
•Titrimetric method
•Chromatographic method
•Microbial assays
Detected by UV
By using RP-Columns
Chromatographic separation
Formulation matrix
Extract drug with solvents

30. 4.MICROBIALASSAYS
Microbial assays are recommended for preparations containing
antibiotics such as:
•Amphotericin-B
•Bacitracin
•Chlortetracycline HCl
•Gentamycin sulphate
Method:
•Cylindrical plate or plate assays
•Turbidimetric or tube assays
5.IMPURITIES:
The impurities arising from degradation of drug substance and during
the manufacturing process of drug product should be assessed and
controlled

31. II.SPECIFIC TESTS:
1.PH
•Creams and ointments contain very limited quantities of water or
aqueous phase,
•Hence this test is not always warranted.
•Formulation dependent.
•Not included in compendia drug product monograph.
2.APPARENT VISCOSITY:
•Formulation and/or process dependent.
•Not included in compendia drug product monograph.

32. 3.UNIFORMITY OF DOSAGE UNIT:
This test is applicable for dosage forms packaged in single unit containers.
4.Water Content:
Determined by Titrimetric methods.
Reagent: KF reagent
Preparations Max., allowable Limit of water
Ointments 0.5 to 1.0%
Bacitracin, Nystatin,
Chlortetracycline HCl ointment
NMT 0.5%
Amphotericin-B, Gentamycin
sulphate, Neomycin sulphate,
Erythromycin sulphate, Tetracycline
HCl
Upto 1%

33. 5.ANTIMICROBIAL PRESERVATIVE EFFECT:
Method: Pour plate technique
Solns of different samples
Mixed with Tryptone Azolectin(TAT) broth separately
Add all cultures into each mixture
Incubate & count no. of organisms on 7,14, 21, 28 days of
incubation

34. On 14thday No.of vegetative cells NMT 0.1%
of intial conc
On 28th day No, of organisms should be below
or equal to intial conc
6.PARTICLE SIZE DETERMINATION:
•Dilute preparation with equal volume of glycerol/ liquid paraffin as per
monograph.
•Mount on glass slide.
•Observe through microscope.
•Calculate the no. of particles having max., diameter within stated limit.

35. III.SPECIFIC TESTS FOR SEMISOLID DOSAGE FORMS:
1.PHASE SEPARATION TEST:
•Visual tests.
•Done by measuring the volume of separated phases.
2.UNIFORMITY IN CONTAINERS:
Type Assay Limit
Multiple dose products containing
>5gm
90-110% of product label
Multiple dose products containing
<5gm
90-110% of product label

36. Procedure:
•Expose the product in tube.
•Visually inspect product.
•Remove a sample of product from top, middle and bottom portions
of the tube.
•Perform assay separately
Products Packaged In Containers Other Than Tubes:
•Select a syringe such that it reaches bottom of the container.
•Remove plunger & cut of bottom of syringe barrel.
•Sample from one side of container is slowly withdrawn by slowly
inserting syringe barrel into container until it reaches bottom.

37. •Twist syringe barrel containing sample core and remove barrel.
•Insert the syringe plunger and carefully extrude the equal portions
representing Top, middle, bottom of container.
•Perform assay separately for each portions

38. INVITRO DRUG RELEASE STUDIES:
These studies are conducted in order to ascertain the release of drug from
the formulation matrix.
Apparatus: Franz diffusion cell

39. Add equal vol. of fresh medium after each sampling
Withdraw samples from receiver side in different time intervals
Phosphate buffer PH 5.4
Receiver side is filled with known volume of release medium
Heat to 0.5oC by circulating water
Known qty of test product is applied uniformly over
the membrane on donor side

40. CONCLUSION:
From this it can be concluded that, though a no. of quality control
tests have been assigned for sold & semisolid dosage forms in IP, BP,
USP yet there occurs some difference between them.
Hence in order to overcome that, the different tests & limits
specified in different pharmacopoeias have to be streamlined and
harmonized in such a way that, tests meets specified limit as per
harmonized one and later meets regulatory requirements of that
particular country.

41. REFERENCES:
1.The controller of publication . Indian pharmacopoeia 5th edition. New Delhi
Ministry of health and family welfare. Indian; 2007 volume I.
2.Published on behalf of medicines and Health Care Products Regulatory Agency;
The department of Health, Social servicesand public safety, British Pharmacopoeia
6th edition. Great Britain; 2010. Volume II.
3.United States Pharmacopoeia 29 National Formulary 24(united States
Pharmacopoeia 29-NF) supplement I, is current from April 1, 2006 through July
31,2006.
4.Prescott, J.K., and Barnum R.A., On Powder Flowability, Pharmaceutical
Technology, October 2000, PP. 60-84 and 236.
5.Baxter, Thomas J., “When Powders Flow Like Water”:Addressing two phase
flow effects in tablet press feed system,” Tablets & Capsules, march 2009, volume
7. No: PP 26-32.