Quality Control Tests of pharmaceutical

dosage forms
1. Capping & Laminating:

o These two defects occur during the ejection stage of the

manufacturing process.
❑ Capping describe the partial or complete separation of the top or
bottom from the main portion of the tablet & comes off as a cap.
❑ Lamination: is the separation of a tablet into two or more-distinct
layers.
o Appear immediately after compression or occur hours or even days,
later.
Reasons of capping :
1. excessive fines in the granulation or lack of sufficient clearance
between punch and die wall
2. In new punches and dies that are tight fitting.
3. Too much or too little lubricant or excessive moisture
1. Capping & Laminating:

Solutions for capping & laminating:

1. Increasing the binder.
2. Adding dry binder such as gum acacia, PVP or powdered sugar.
3. Decreasing or changing lubrication.
4. Decreasing the upper punch diameter

❑ PROBLEM: Dry granules can cap or laminate due to lack of cohesiveness.

Solution: In moisture-critical granulations, adding a hygroscopic material
like sorbitol, methylcellulose, or PEG 4000 can assist maintain an
appropriate moisture level.
❑ Problem: deep concave punches produce tablets that cap (the curved section
extends radially while the body cannot, creating a shear force that fractures).
❑ Solution: Flat punches may eliminate this additional shear stress.
2. Sticking, Picking & Filming:
▪ Adhesion of the material to the punch faces.
Sticking : (whole adhesion)
▪ Is usually due to improperly (incorrectly)
dried or lubricated granulation causing the
whole tablet surface to stick to the punch
faces → dull, scratched, or rough tablet
faces.
❑ Picking : (localized adhesion)
▪ Is a form of sticking in which a small portion of
granulation sticks to the punch face & a portion
of the tablet surface is missed.
2. Sticking, Picking & Filming:
❑ Filming: is a slow form of sticking and is largely due to excess
moisture in the granulation, high humidity, high temperature, or
loss of highly polished punch faces due to wear.

These may be overcome by:

o Decreasing the moisture content of the granulation.
o Polishing the punch faces.
o Cleaning and coating the punch faces with light mineral oil
3. Mottling:

▪ It is an unequal distribution of color on the

tablet surface with light or dark areas
standing out in an otherwise uniform surface.
Reasons of Mottling :
1. A drug is differing in color from its
excipients or whose degradation products
are highly colored.
2. Migration of a dye during drying of a
granulation.
To overcome this difficulty: The formulator may →
o change the solvent system, o change the binder system
o grind to a smaller PS o reduce the drying temperature
4. Chipping and Cracking:
❑ Chipping: Breaking of tablet edges, while the
tablet leaves the press or during subsequent
handling and coating operations.
❑ Reasons of Chipping
1. Incorrect machine settings, especially mis-set
ejection take-off.
2. These problems are similar to those of capping
and laminating and are annoying and time
consuming.
❑ Cracked tablets are usually cracked in the upper
and lower central surface of the tablets or very
rarely on the side wall.
4. Chipping and Cracking:

Causes of cracking
• It often occurs where deep concave punches are used.
• Large size of granules
• Too dry granules
• tablets expanding
Solutions for Chipping & Cracked :
• Polishing punch faces.
• Replacing nicked or chipped punches.
• Reducing fines.
• Adding dry binder such as pregelatinized starch, gum
acacia, PVP,
 Size and S.D Before Compression
Poor Flow..
Weight Variation. Poor Mixing.
Punch Variation

o Tablet weight is determined by amount of granulation in the die

before compression.
o Anything that can alter the die-filling process can alter tablet
weight and weight variation.
A. Granule Size and Size Distribution Before Compression.
▪ variations in the ratio of small to large granules and the size
difference between them. → Influence how the void spaces between
particles are filled
1. Using large granules in a small die cavity (minimal granules are
needed) may result in a considerable weight variation.
2. If die fill requires hundreds of granules on average, (a few
granules around the average would cause slight weight variation
given a narrow particle size range).
Weight Variation.
B. Poor Flow..
▪ Die-fill depends on continuous, uniform granulation flow from the
hopper through the feed frame.
1. Granulation moves spasmodically through the feed frame
when it doesn't flow easily, leaving certain dies unfilled.
2. When machine speed exceeds granulation flow, dies are not
properly filled.
▪ Solution:
1. Addition of a glidant
2. Induced die feeders
Hardness Variation.
Hardness depends on:
1. Weight of material
2. Space between the upper and lower punches at the moment
of compression.

If the volume of material or the distance between punches varies

hardness is inconsistent.
Double Impression.
This only involves monogrammed or engraved punches.
❑ Problem: The punch imprints the tablet during compression. On
some machines, the bottom punch drops and travels
uncontrolled for a short distance before riding up the ejection
cam to drive the tablet out of the die.
o During its free travel, it rotates.
▪ At this point, the punch may produce a lighter impression
on the tablet's bottom, creating a double imprint.
▪ Solution:
o Newer presses have anti-turning systems built in.
Tablets evaluation
▪ To evaluate a tablet product in terms of :
1. General appearance
2. Weight variation
3. Friability
4. Disintegration test
5. Dissolution rate
6. Hardness
7. Content uniformity
8. Thickness
Tablets evaluation

→ It done by quality control department (Q.C.)

Role of Q.C. department

▪ It a small part of quality assurance (QA-) that concerned with
sampling, testing and documentation during and after
completion of manufacturer.
▪ QC involves production steps to ensure product quality and
reproducibility.
▪ It monitors the product after manufacture and compares it to
standards to find out why it deviates, ensuring quality every
time.
Quality control steps for tablet
1. General appearance
a. Size, shape and thickness
▪ This is important to facilitate packaging and to decide
which tablet compressing machine to use.
Tablet thickness (dimensional variation) related to:
• Constant compression load: tablet thickness varies with
tablet weight, die fill and particle size distribution.
• Constant die fill: thickness varies with compression load.
b. Organoleptic properties:
▪ It include color, taste and odor of the tablets
Quality control steps for tablet
1. General appearance
a. Size, shape and thickness
▪ It can be controlled by size and shape of
punches and die of tab. machine
▪ Compressed tablets vary greatly in shape
that could be round, oblong, or triangular.
▪ Tablets can be flat or convex depending on:
− the punches' contours: flat face,
shallow cup, regular cup, deep cup, or
modified ball.
▪ Tablets can be scored in halves, thirds, or quadrants → This
facilitates precise tablet breaking for partial administration.
▪ Scored tablets usually have one groove.
Quality control steps for tablet
1. General appearance
Tablet thickness (dimensional variation)
▪ The allowed limit of thickness variation is ± 5% of the size
of the tablet.
▪ Variation in tablet thickness leads to → counting and
packaging problems.
▪ Thickness of the tablet depends on
▪ the density of granulation,
▪ the pressure applied to the tablet
▪ the speed of tablet compression.
Quality control steps for tablet
1. General appearance
Tablet thickness (dimensional variation)
▪ It is determined with:.
a) Micrometer→ It measure individual tab.
thickness
o It Permits accurate measurements
o Give information on variation between tab.
b) Holding tray: → it measures total tab.
thickness (5-10 tablets) using a sliding caliper
scale,
▪ It is not accurate → provides estimates rather
than tab-specific information
▪ It more rapid than a micrometer .
Organoleptic properties:
a. Color (rapid identification and consumer acceptance).
Adv.: The color of a product must be uniform within a single tablet also from
tablet to tablet, and from lot to lot.
Disadv.:
1. Nonuniformity (“mottling”) of color can lacks esthetic appeal.
2. Consumer can recognize nonuniformity of content and general
poor quality of the product.
o Eye: cannot discriminate small differences in color nor can it
precisely define color
o Machines like:
▪ Microreflectance photometer (measure the color uniformity
and gloss on a tablet surface).
Organoleptic properties:
b. Odor (indicate a stability problem)
Examples:
1. Odor of acetic acid (degrading aspirin tablets).
2. Odor of the drug (vitamins have a characteristic odor).
3. Added ingredients (flavoring agents have pleasant odors).
4. The dosage form (film-coated tablets usually have a
characteristic odor).
c. Taste (important in consumer acceptance of chewable
tablets).
▪ Many industries use taste panels to evaluate flavour levels
Tablet hardness: Nonofficial test:
▪ It is the force required to break a tablet in a diametric compression
test.
Tablets needed a certain amount of strength and resistance to friability
to:
1. Withstand mechanical shock of handling in manufacture,
packaging and shipping.
2. Tablets must withstand usual user abuse.
▪ Tablet hardness usually affects drug dissolution and release, and it
may affect bioavailability
▪ Unit of hardness is expressed in kg Hardness of different
▪ Ordinary tab. 4-8 kg tablets types
▪ Chewable tab. 3 kg to prevent harmful effect on teeth
▪ Lozenges (troches) and sustained release 10-20 kg
Methods for hardness measurement

A. Tablet strength was tested by breaking it between the second and third
fingers with the thumb as a fulcrum. → Tablets with a “sharp” snap have
acceptable strength.

(simple, low cost and rapid)

(manual)

It is digital instrument in which the force is

applied electrically. It gives more
reproducible results
Hardness of tab like its thickness is a function of:

(Die fill constant) → then additional compression force

result in more hardness and less thickness

(Compression force constant–fixed distance between

upper and lower punches) → then hardness ↑ with ↑ in
die fill and ↓ with lower die fill.

Quantity and quality of binder (good binder result in

appropriate tab hardness and not hinder the release of
drug from tab.).

Lubricant can affect tab hardness

→ if too high conc. or long time mixing

N.B. Tablets are harder several hours after compression than immediately after
compression.
Friability (abrasion and shock)
Nonofficial test:
o It evaluate the ability of tablets to withstand abrasion,
packaging, handling and shipping.
o It also the phenomenon whereby tablet surfaces are damaged
and/or laminated or broken when subjected to mechanical
force or attrition.
Factors affecting friability:
1. Addition of large amount of fine powder to the formula.
2. Over drying of granules (moisture content).
3. Use of material that is not cohesive to the formula.

o Some chewable and most effervescent tablets are highly

friable and require special unit packaging
Laboratory friability tester:

1. Roche friabilator
▪ 20 tablets are dusted, weighed then drop into a plastic
chamber revolves at 25 rpm.
▪ A pre-weigh tabs are inserted in the friabilator from a
distance of 6 inches with each revolution,
▪ operated for 100 revolutions (4 minutes), then dusted, and
reweighed (only the intact ones).
▪ Friability (weight loss) < 0.5% - 1% is acceptable.
Initial weight − Final weight after rotation 4 min .
% Friability =  100
Initial weight
Laboratory friability tester:

o When capping observed on friability testing the tab should not

be used commercially, regardless of loss percentage.
o The moisture content of tab granulation and finished tabs might
affect friability → Low but acceptable moisture acts as a binder,
whereas too-dry granulation produces more friable tabs.
Pharmacopeial or official tests:
A- Weight variation
▪ Weight variation test applies to tablets containing 50 mg or
more drug or when the drug represents 50% or more by weight
of the dosage form unit.
Procedure
o 20 tabs weigh and calculate the average weight
o Each tablet is then weighed individually
o Calculate % of deviation for each tablet according to the Formula.
% Deviation = [(weight of tablet – mean) / mean ] × 100
o no more than 2 tabs should be outside percentage limit (i.e. 18 tablets
within ± 10, 7.5 and 5% and 2 tablets within ± 20, 15, 10%).
o The limited weight variation according to USP:
Average wt. (mg) Less than 130 mg 130-324mg >324 mg
Allowance ±10% ±7.5% ±5%
Pharmacopeial or official tests:
Weight variation
Accepted tablet:
▪ Not more than two tablets are outside the percentage limit and
no tablet differ by more than two times the percentage limit
according to the above table.
Rejected tablets:
▪ One tablet differs by more than two times the percentage limit
according to the table.
▪ More than six tablets are outside the percentage limit.
Factors affecting wt. variation:
o Segregation of the powder
o Poor mixing, and Poor flow
o Variation in the adjustment of the upper and lower punch
o Use of insufficient quantity of lubricant
Pharmacopeial or official tests:
Weight variation
Notes :
o The weight variation test can not ensure uniform potency of
moderate- or low-dose medication tablets (excipients make up most
of the tablet weight).
o The test not carried out for coated tablets due to the content of
coating materials are not calculated.
o The test indicates the uniformity of drug content if the drug content
is more than 50 mg
o Coated tablets are exempt but must pass the content uniformity test if
applicable.
 Problem 1
Solve the following
o The tablet below provides the weight of each of 20 tablets sampled
during drug production for in-process weight variation test (tablet
specified weight is 300 mg). Guided by the USP, state whether this
given batch will be accepted or rejected.
o Justify your answer.

Tablet 1 2 3 4 5 6 7 8 9 10

Weight
286 305 311 300 307 290 310 314 311 304
(mg)

Tablet 11 12 13 14 15 16 17 18 19 20

Weight
301 299 309 289 295 301 287 313 291 307
(mg)
 Solution
Tablet 1 2 3 4 5 6 7 8 9 10
Weight (mg) 286 305 311 300 307 290 310 314 311 304
Tablet 11 12 13 14 15 16 17 18 19 20
Weight (mg) 301 299 309 289 295 301 287 313 291 307

Average Percentage of Lower limit of Upper limit of

weight deviation deviation deviation
300 mg 5% 285 315

Double limit of Double lower limit of Double upper limit of

deviation deviation deviation
10% 270 330

No. of tablets No. of tablets Approval of batch

within limit without limit 32

20 0 Accepted
Disintegration test
▪ For a drug to be readily
available to the body, it must
be in solution.
▪ For most tablets, the first
important step toward solution
is break down of the tablet into
smaller particles or granules, a
process called disintegration
▪ Disintegration time: is the
time required for the tablet
to break into particles
Disintegration test
❑ The disintegration test assesses simply the time it takes a group of
tablets to break down into particles that can pass through a 10-mesh
screen under certain conditions.
❑ Complete disintegration: is a state in which any residual is a soft
mass with no firm core except insoluble coating fragments on the
apparatus's screen.
Generally, the disintegration time is as follow:
1. For uncoated tablets is 30 minutes.
2. For coated tablets is 1 hour.
3. For soluble tablets and effe. Tab. should disintegrate within 3 min.
4. Enteric-coated tablet should not disintegrate in SGF (2 hour) but
should disintegrate in simulated intestinal fluid in 2 hours.
5. Chewable tablets are not subjected to the disintegration test.
U.S.P. disintegrator
o Consists of a rack holding 6 glass or
plastic tubes each of 3 inches long;
open at the top and having a 10-mesh
screen at its bottom.
o The basket containing the tablets up
and down through a distance of 5-6
cm at a fixed rate (30 cycle/ min.) in
the fluid maintained at 37 ± 2°C
(body temp) by a water bath.
o Six tablets are placed one in each
tube along with a plastic disk over
each tablet (to prevent tablet floating
and impart a slight pressure on the
tablet to force any soft mass through
the screen).
Disintegration test
Liquids used in disintegration
o Water,
o Simulated gastric fluid (pH = 1.2 HCl), or Sim. intestinal fluid
Factors affecting the disintegration time
1. Content: especially the quantity and quality of the disintegran
t and lubricant (mixing condition and time of addition).
2. Hardness: amount of binder , compression force.
3. Design of granulation procedure which will affect the
physical properties of the granules.
Content uniformity test:
o This test to ensure that every tablet contains the labeled amount
of the drug within the prescribed limits (generally ±15%).
USP method :
1. Take 10 tablets from random samples of 30 tablets and
assay.
→ If only one tablet deviate from USP limits ± 15 %
(85%-115%)
2. Select another 30 tablets and assay individually
▪ The batch are accepted, if Not less than 29 tablets obey
the limits.
Content uniformity test:
B.P Method:
1. Take 20 tablets randomly, mill and assay the content according
to the procedures in pharmacopeia.
2. Calculate the concentration of drug in 20 tablets and in each
tablet by dividing over 20.
content
% Recovery = × 100.
labeled amount
▪ The B.P permit ± 10% , i.e. the amount of active ingredient must
be 90% - 110%.
▪ The batch rejected if one tablet deviate from limits.
N.B: Content uniformity or wt. variation for highly active ingredient tablets 90-
95% having no problems to calculate.
Content uniformity test:
Factors affecting content uniformity:
1. Non uniform distribution of the
drug in powder mixture or
granulation.

2. Segregation of the powder mixture

or granulation during manufacture
processes. N.B: Small dose drug
having problem of
content uniformity and
wt. variation so each
3. Weight variation of the tablets. calculate individually.
Dissolution test
o For complete assessment of a drug release from tablets (in-
vivo bioavailability should be accomplished) but its use is
restricted, thus in-vitro dissolution test have been used and
developed and it is un-direct measurement of drug availability.

▪ Dissolution is the process by which a solid enters a solution .

▪ This test determines the amount of active ingredient(s) released
from a solid oral dosage form, such as a tablet or a capsule,
using a known volume of dissolution medium within a
predetermined length of time.
▪ The therapeutic effect of different formulations of the same
drug depends on the rates at which the drug is released.
 USP/NF monograph specify:
• The dissolution test medium
• Apparatus to be used
• Time limits of the test
• The assay procedure
• Volume (dissolution medium)
• The speed (rpm) of the test to be performed

This is ideal for capsules and dose • It is generally preferred for tablets.
forms that float or disintegrate slowly.

o For many preparations, the paddle is preferred over the basket.

standardized BP conditions
1. Rotation speed:100 rpm (basket), 50 rpm (paddle)
2. Dissolution medium volume: 900 ml
3. Dissolution medium composition: aqueous, commonly 0.1M
hydrochloric acid or phosphate buffers of pH 6.8 to 7.4
4. Number of units tested: 6 (plus 6, if retest).
▪ When Apparatus I is used, place the tablet at the beginning of each
test. Lower the basket into position before rotation.
▪ Apparatus II allows the tablet to sink to the bottom of the vessel
before rotating the paddle. Tablets float horizontally at the bottom of
the tank if a wire or glass helix is utilized.
Dissolution test
All apparatus parts that may come into contact with the preparation
or dissolution liquid are:→
▪ chemically inert and do not adsorb, react, or interfere with
the preparation being examined.
o All metal parts of the apparatus that may come into contact with
the preparation or dissolution medium must be :→
▪ stainless steel or coated to prevent reaction or interference.
o Pharmacopoeial tests employing the basket or paddle operate
under ' sink conditions', so material already in solution does not
affect the remainder's dissolution rate.
o 'Sink conditions' occur in a volume of dissolution media 5–10
times saturation volume.
 Acceptance criteria(BP2005)
▪ The batch will be accepted if not less than 70% of the labeled
drug content of each tablet from 6 tablets tested have released
(dissolved) within 45 minutes.
▪ If one or two tablets fail the test, 6 more tablets are tested.
→ At least 10 of the 12 tablets must meet the
requirements.
▪ The dissolution results are plotted as concentration versus time.
▪ The choice of a time is, of necessity, somewhat random but 45
minutes is considered satisfactory for most conventional-release
(non-modified-release) products
 Dissolution testing and interpretation IP standards

Test tolerance (Q)

o Is expressed as a percentage of the labeled amount of the drug dissolved in the
time limit
S. Quantity Number of Acceptance criteria
no. Stage/level tablets tested
1 S1 6 Each unit not less than Q* + 5
percent**
2 S2 6 Average of 12 units (S1 +S2) is equal
to or greater than (>)Q, and no unit is
less than Q - 15 percent**
3 S3 12 Average of 24 units (S1+S2+S3) is
equal to or greater than (>)Q, not more
than 2 units are less than Q-15
percent** and no unit is less than Q-
25 percent**
− *Q is the amount of dissolved active ingredient specified in the individual
monograph, expressed as a percentage of the labelled content.
− ** Percentages of the labelled content.