Quality control

of tablets
 Dissolution
 It is a routine quality control procedure. The dissolution rates also
.helps to correlates the bioequivalence of drug products

 To ensure that the preparation comply with product specification, as it

is a requirement for regulatory approval of marketing for the registered
.product

 To indicate the performance of the preparation under the in vivo

.conditions

To differentiate between formulations and to evaluate the possible

effect of the formulation and other processes variables on drug
.bioavailability
 Factors affecting dissolution of a tablet
.Disintegration is the important first step to drug dissolution in a tablet .1

.Particle size of drug substance .2

Solubility and hydrophobicity of the drug; type and amount of .3

disintegrant, diluent, binder, lubricant, glidant and the coating type and
.thickness

Solubility and dissolution also influenced by pH of the media, media .4

.composition, change in the crystalinity of drug, temperature, paddle speed

Manufacturing method (compactness of the granulation and compression .5

force used in tableting)
.Dissolution test is a standard requirement for tablets and capsules
USP gives standards for tablet dissolution; there are many apparatus for drug release and drug
.dissolution for immediate release, extended release and enteric-coated tablets
• The rate of dissolution is given by Noyes and
Whitney:
dc = k (Cs- Cb)
dt
Where,
dc/dt= dissolution rate of the drug
K= dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution
at time t
4
 Dissolution test apparatus

Stirrer shaft Glass vessel

USP apparatus II
Paddle Thermostated water bath
 Stirrer shaft

Cylindrical Stainless Paddle Glass vessel 1000 ml volume

steal Basket formed )USP apparatus II(
from a screen
)USP apparatus I(
 Stirred vessel method

Basket type Paddle type

Media used in dissolution test:

- Purified water.
- Simulated gastric fluid.
- Simulated intestinal fluid.
- Solvents mixture may be used if the drug solubility is very
low.

 Dissolution test is performed in-process and on the final

.product
 The amount of drug dissolved within a certain time period is •
determined by taking samples from the dissolution medium and
analyzed after specified time intervals.

• Limit (BP): 75% of the drug should be dissolved within 30

.minutes, unless otherwise specified by the manufacturer
:Acceptability criteria for immediate release tablets (USP)

Acceptance Criteria Units Stage

Each unit is not less than Q + 5% 6 S1
Average of 12 units (S1 + S2) is equal to or greater than Q, and no unit is 6 S2
less than Q-15%.
Average of 24 units (S1 + S2 +S3) is equal to or greater than Q, not more 12 S3
than 2 units are less than Q-15%, and no unit is less than Q-25%.

Q, is the amount of dissolved active ingredient specified in individual monograph,

.expressed as percentage of labeled content of dosage unit
 Friability test

?Why measure friability

:Tablets that tend to powder, chip & fragment when handled

.lack elegance & consumer acceptance .1
Create excessive dirt/ dust in areas of manufacturing as coating & .2
.packaging
Can also add to a tablet's weight variation or content uniformity .3
.problems
Another application of the friability test
capping or laminate when stressed by attrition inside the rotating
.drum of friability tester
Capping Lamination

Good tablet
 The laboratory friability tester is known as the Roche friabilator.
 To examine this, tablets are subjected to uniform tumbling motion for
specified time and weight loss not more than 1% generally is considered
acceptable for most products.
% friability = (W0 – Wf / W0) x %.
W0 = initial weight.
.Wf = final weight

Friabilty tester
:Number of tablets selected for friability test

Tablet unit weight less than ≤ 650 mg: Take a sample of whole tablets as near as
.possible to 6.5 g

Tablet unit weight more than or equal > 650 mg: Take a sample of whole 10
.tablets

Tablets damaged during friability testing

 II. Unofficial tests
There are many tests are frequently applied to tablets for which
there are non-pharmacopoeial requirements but will form a part of
manufacture's owner product specifications.
1- Tablet thickness.
2- Tablet hardness.

1. Hardness (Fracture-resistance test):

 In general, tablets should be sufficiently hard to resist breaking

during normal handling, packaging and shipping, and yet soft enough to
disintegrate properly after swallowing.
 Hardness of the tablet is controlled by (or is affected by) the degree of
the pressure applied during the compression stage.
 Hardness is an important criterion, since it can affect disintegration
.and dissolution
Tablet Hardness: The force required to break a tablet along its diameter
by applying compression loading.
Determine the crushing strength of the tablets. The crushing strength
that just causes the tablet to break is recorded (in kg). Tablet hardness
.should be between 6 – 10 kg

Tablet hardness tester The Electronics Tablet Hardness tester

 If the tablet is too hard, it may not disintegrate in the
required period of time to meet the dissolution
specifications; if it is too soft, it may not be able to
withstand the handling during subsequent processing such
as coating or packaging and shipping operations.

 Chewable tablets are usually much softer (3 kg) and

some sustained release tablets are much harder (10-20 kg).

 Hardness Variation depends on

- compression force,
- concentration and type of binding agent
Tablet thickness .2

Tablet thickness is important for tablet packaging; very thick tablets

affect packaging either in blisters or plastic containers. The tablet
thickness is determined by the diameter of the die, the amount of fill
permitted to enter the die and the force or pressure applied during
compression

Micrometer (tablet thickness)

 Tablet processing problems
Capping and lamination -1
Picking and sticking -2
Tablet mottling -3
Binding -4

:Capping and lamination .1

 Capping occurs when the upper segment of the tablet separates from
.the main portion of the tablet & comes off as a cap
Is a partial or complete separation of the top or bottom crown of tablet from the main
body

. Lamination that the tablet splits at the sides into two or more distinct layers
.If tablets laminate only at certain stations, the tooling is usually the cause
These problems are readily apparent immediately after compression. Friability is the earlier and
.quickest way of revealing such problems
These problems are usually caused by:
- Air entrapment during compression process among the particles or granules, the resulting
tablet expand when the pressure of the tableting is released, resulting in splits or layers in
the
.tablet

Rapid decompression results in tablets that fracture (stress-relaxation) -

If the compression is too rapid, air is not given time to escape but remains trapped within
the tablet until released by removal of the pressure. Excessive pressure cause slight
.expansion of the tablet after the pressure is released and capping might occur

Excess amount of lubricant which may decrease the tablet strength due to their -
interference
.with the bonding between the particles during compression

The binder may be insufficient in amount or unsuitable . Therefore, the granules will be -
.friable and lacking in cohesion

Overdrying of granules (granules require a certain moisture content, to assist the action of -
the binder in producing a firm tablet).
- In new punches and dies that are tight fitting this may occur with new sets of tools, when
.the air in the granule cannot escape between the upper punch and the die wall
 A deep Concave punches produce tablets that cap. The curved part of such tablets expands -
.while the body of the tablet cannot, which establishes a shear stress that produces the fracture

Incorrect setup press. If the punch remains below the face of the die, the sweep-off blade -
cuts off the tablet, leaving the bottom in the die.
- An incorrect adjustment of the sweep-off blade can also result in tablet fracture.

Elimination of capping & laminating:

1. Increasing the binder.

2. Adding dry binder such as gum acacia , PVP or powdered sugar.
3. Decreasing the upper punch diameter and using flat punches.
4. Slowing the tabletting rate.
5. Reducing the final compression pressure.
6. For moisture-critical granulations, the addition a hygroscopic
substance e.g. methylcellulose or polyethylene glycol PEG4000, can
.help to maintain proper moisture level
Picking is the removal of the surface material of the tablet by the punch (a portion -2
of the tablet surface is missed). Sticking is the adhesion of the tablet materials to the
die wall (dull, scratched, or rough tablet faces). These problems are caused by
excessive moisture or the inclusion of materials with low melting point (PEG &
stearic acid) in the formulation. This problem could be managed by addition of
. suitable anti-adherent. Increase lubrication
Additional binder may make the granules more cohesive. Colloidal silica added to the
formula acts as a polishing agent and makes the punch faces smooth. Dilution of the
active ingredient with additional higher melting point materials and consequent
.increase in the size of the tablet may help

Picking Sticking
Tablet mottling is unequal color distribution, with light or dark areas. -3
This problem occurs when a drug has different color than the tablet
excipients or when a drug has colored degradation products. This
problem also caused by intragranular migration of the soluble dye during
the drying stage which may give rise to dry granules with a highly
colored outer zone and interior. During compaction granules are
.fractured and the colorless interior is exposed resulting in mottled tablet
To overcome this difficulty, change the solvent and binder system, reduce the drying
.temperature, grind to smaller particle size
Migration of colors may be reduced by drying the granulation -
slowly at low temperatures and stirring the granulation while
.drying
Addition of natural starches, or dye migration inhibitors such as -
acacia 3%, tragacanth 1%
.and talc 7%
Using dye lakes (combination by adsorption of a water-soluble -
dye to a hydrous oxide of a heavy metal resulting in an
insoluble form of the dye)