In-process Quality Control of Tablet

In-process Quality Control of Tablet

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1.0 Introduction

IPQC or IN PROCESS QUALITY CONTROL are the checks that are carried out during
the manufacturing process with a regular time interval. The function of in-process controls
is monitoring and if necessary adaption of the manufacturing process in order to comply
with the specifications .this may include control of equipment and environment too. In-
process materials should be tested for identity, strength, quality and purity as appropriate
and approved or rejected by the quality control unit during the production process.
Rejected in-process materials should be identified and controlled under a quarantine
system designed to prevent their use in manufacturing

In manufacturing of tablet dosage forms, a number of quality control tests are performed
to ensure that tablets produced meet the requirements as specified in official Monograph
(BP or USP). These tests can be grouped into two broad categories namely:

1. Pharmacopoeial or Official tests

a. Weight variation
b. Disintegration
c. Dissolution
d. Content Uniformity

2. Non-pharmacopoeial or Non-official tests

a. Hardness
b. Friability

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Stage wish In-process Checks during tablet manufacturing process

1. In-process test during granulation:

a. Loss on drying
b. Bulk density
c. Tap Density
2. In-process checks during Compression
a. Appearance
b. Weight Variation
c. Hardness Variation
d. Thickness, Diameter Variation
e. Friability
f. Disintegration
g. Dissolution
h. Content Uniformity (QC Test)

In-process Test during Granulation

Loss on drying:

Equipment Name: Moistures Analyser

Equipment details: A moisture analyser comprises two elements - a heating unit and a
weight balance. The sample is first weighed accurately, before being heated. The
temperature is typically kept below the melting point and below the point of degradation.
The heating is accomplished using a halogen lamp which emits infrared radiation to dry
the sample very quickly. The wavelength of the radiation is such that much of it is
absorbed by the sample, and thus the temperature of the material may be above that
which is displayed, which is that expected from surface heating by infrared radiation.

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Figure1, Moisture Analyzer

Principle of Equipment: The principle of the thermogravimetric method of moisture

content determinations defined as the weight loss of mass that occurs as the material is
heated. The sample weight is taken prior to heating and again after reaching a steady-
state mass subsequent to drying.

Procedure: Mix and accurately weigh the substance to be tested, and, unless otherwise
directed in the individual monograph, conduct the determination on 1 to 2 g. If the test
specimen is in the form of large crystals, reduce the particle size to about 2 mm by quickly
crushing. Tare a glass-stoppered, shallow weighing bottle that has been dried for 30
minutes under the same conditions to be employed in the determination. Put the test
specimen in the bottle, replace the cover, and accurately weigh the bottle and the
contents. By gentle, sidewise shaking, distribute the test specimen as evenly as
practicable to a depth of about 5 mm generally, and not more than 10 mm in the case of
bulky materials. Place the loaded bottle in the drying chamber, removing the stopper and
leaving it also in the chamber. Dry the test specimen at the temperature and for the time
specified in the monograph. Upon opening the chamber, close the bottle promptly, and
allow it to come to room temperature in a desiccator before weighing.

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If the substance melts at a lower temperature than that specified for the determination
of Loss on drying, maintain the bottle with its contents for 1 to 2 hours at a temperature

5 to 10 below the melting temperature, then dry at the specified temperature.

Calculation:

% of moisture is calculated by,

% moisture content = Initial wt. - Final wt./ initial weight X 100

Bulk Density :
The bulk density of a powder is the ratio of the mass of an untapped powder sample and
its volume including the contribution of the interparticulate void volume. Hence, the bulk
density depends on both the density of powder particles and the spatial arrangement of
particles in the powder bed. The bulk density is expressed in grams per millilitre (g/mL)
although the international unit is kilogram per cubic meter (1 g/mL = 1000 kg/m3 )
because the measurements are made using cylinders. It may also be expressed in grams
per cubic centimetre (g/cm3 ). The bulking properties of a powder are dependent upon
the preparation, treatment and storage of the sample, i.e. how it was handled. The
particles can be packed to have a range of bulk densities and, moreover, the slightest
disturbance of the powder bed may result in a changed bulk density. Thus, the bulk
density of a powder is often very difficult to measure with good reproducibility and, in
reporting the results, it is essential to specify how the determination was made. The bulk
density of a powder is determined by measuring the volume of a known mass of powder
sample, that may have been passed through a sieve into a graduated cylinder

Procedure: Pass a quantity of powder sufficient to complete the test through a sieve with
apertures greater than or equal to 1.0 mm, if necessary, to break up agglomerates that
may have formed during storage; this must be done gently to avoid changing the nature
of the material. Into a dry graduated cylinder of 250 ml (readable to 2 ml), gently introduce,
without compacting, approximately 100 g of the test sample (m) weighed with 0.1%
accuracy. Carefully level the powder without compacting, if necessary, and read the
unsettled apparent volume (V0) to the nearest graduated unit. Calculate the bulk density
in (g/ml) using the formula m/V0. Generally, replicate determinations are desirable for the
determination of this property. If the powder density is too low or too high, such that the
test sample has an untapped apparent volume of either more than 250 ml or less than
150 ml, it is not possible to use 100 g of powder sample. Therefore, a different amount of
powder has to be selected as test sample, such that its untapped apparent volume is 150
ml to 250 ml (apparent volume greater than or equal to 60% of the total volume of the

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cylinder); the mass of the test sample is specified in the expression of results. For test
samples having an apparent volume between 50 ml and 100 ml a 100 ml cylinder
readable to 1 ml can be used; the volume of the cylinder is specified in the expression of
results.

Tap Density:
The tapped density is an increased bulk density attained after mechanically tapping a
container containing the powder sample. The tapped density is obtained by mechanically
tapping a graduated measuring cylinder or vessel containing the powder sample. After
observing the initial powder volume or mass, the measuring cylinder or vessel is
mechanically tapped, and volume or mass readings are taken until little further volume or
mass change is observed. The mechanical tapping is achieved by raising the cylinder or
vessel and allowing it to drop, under its own mass, a specified distance by either of three
methods as described below. Devices that rotate the cylinder or vessel during tapping

Method:
Apparatus. The apparatus (Figure 1) consists of the following: — a 250 ml graduated
cylinder (readable to 2 ml) with a mass of 220 ± 44 g; and — a settling apparatus capable
of producing, in 1 minute, either nominally 250 ± 15 taps from a height of 3 ± 0.2 mm, or
nominally 300 ± 15 taps from a height of 14 ± 2 mm. The support for the graduated
cylinder, with its holder, has a mass of 450 ± 10 g.

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Figure2, Tap Density Apparatus

Procedure. Proceed as described above for the determination of the bulk volume (V0).
Secure the cylinder in the holder. Carry out 10, 500 and 1250 taps on the same powder
sample and read the corresponding volumes V10, V500 and V1250 to the nearest
graduated unit. If the difference between V500 and V1250 is less than or equal to 2 ml,
V1250 is the tapped volume. If the difference between V500 and V1250 exceeds 2 ml,
repeat in increments such as 1250 taps, until the difference between succeeding
measurements is less than or equal to 2 ml. Fewer taps may be appropriate for some
powders, when validated. Calculate the tapped density (g/ml) using the formula m/Vf in
which Vf is the final tapped volume. Generally, replicate determinations are desirable for
the determination of this property. Specify the drop height with the results. If it is not
possible to use a 100 g test sample, use a reduced amount and a suitable 100 ml
graduated cylinder (readable to 1 ml) weighing 130 ± 16 g and mounted on a holder
weighing 240 ± 12 g. The modified test conditions are specified in the expression of the
results.

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Appearance:
Size and Shape
The size and shape of the tablet should be according to need of the dose requirement
and can be dimensionally described monitored and controlled. It is determined by the
tooling during the compression processes.
Color and Odor
For ease of identification many pharmaceutical tablets use color and it also helpful for
consumer acceptance. But it must be uniform within a single tablet, from tablet to tablet
and from batch to batch. Stability problem may be indicated by odour in batches of tablets
e.g. vitamins have a characteristic odour. For the chewable tablet taste is importance
factor for consumer acceptance.
Unique Identification Markings
Pharmaceutical companies often use some type of unique markings on tablets in addition
to color, for rapid identification of their product these markings utilize some form of
embossing, engraving or printing of the company name or symbol or a product code.

Weight Variation
Weigh 20 tablet selected at random, each one individually. X1, X2, X3… Xz
Determine the average weight. X= (X1+X2 +X3+…+ Xz)/20

Limit:
Upper limit = average weight + (average weight * % error)
Lower limit = average weight - (average weight * % error)
The individual weights are compared with the upper and lower limits.
Not more than two of the tablets differ from the average weight by more than the % error
listed, and no tablet differs by more than double that percentage.

Weight Variation Tolerances for Uncoated Tablets

USP STANDARDS
Sr. No Average wt. of Max. % difference
tablet(mg) allowed
1 130 or Less 10%
2 130-324 7.5%
3 More than 324 5%

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BP STANDARDS
Average wt. of Max. % difference
Sr. No tablet(mg)
Average wt. of allowed
Max. % difference
tablet(mg) allowed
1 80 or Less 10%
2 80-250 7.5%
3 More than 250 5%

Thickness
The thickness of a tablet is the only dimensional variable related to the process, Thickness
of tablets measured by a micrometer. Other techniques involve placing 5 or 10 tablets in
a holding tray, where their total thickness may be measured by a sliding caliper scale.
Thickness of tablet should be controlled within a ± 5 % variation of a standard. Thickness
must be controlled

Hardness
Tablet requires a certain amount of strength or hardness and resistance to friability to
withstand mechanical shocks of handling in manufacture, packaging and shipping.
Hardness generally measures the tablet crushing strength.

Test For this test tablet hardness tester is use to check the hardness of the tablet.
Monsanto, Pfizer Schleuniger these are the examples of hardness testers. Monsanto
hardness tester consists of a barrel containing a compressible spring held between two
plungers. The lower plunger is placed in contact with the tablet and zero reading is taken.
The upper plunger is then forced against a spring by turning a threaded bolt until the tablet
fractures. As the spring is compressed, a pointer rides along a gauge in the barrel to
indicate the force. The force of fracture is recorded in kilogram. Ten tablets are crushed
and measure their hardness and the allowable range is between 4 - 6 kg (40 - 60 N)
unless otherwise specified.

Importance
To determine the need for pressure adjustments on the tableting machine.
Hardness can affect the disintegration.
So if the tablet is too hard, it may not disintegrate in the required period of time. And if the
tablet is too soft, it will not withstand the handling during subsequent processing such as
coating or packaging.

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In general, if the tablet hardness is too high, we first check its disintegration before
rejecting the batch.
If the disintegration is within limit, we accept the batch.

Factors Affecting the Hardness

[1] Compression of the tablet and compressive force.

[2] Amount of binder. (More binder à more hardness)

[3] Method of granulation in preparing the tablet (wet method gives more hardness than
direct method, Slugging method gives the best hardness).

Figure3, Hardness test apparatus

Friability:

Friability (the condition of being Friable) testing is a method, which is employed to

determine physical strength of uncoated tablets upon exposure to mechanical shock and
attrition. In simple words, friability test tells how much mechanical stress tablets are able
to withstand during their manufacturing, distribution and handling by the customer.
Throughout pharmaceutical industry, friability testing has become an accepted
technology and the instrument used in to perform this process is called Friabilator or
Friability Tester.

In friability test, samples are counted and weighted then tumbled in rotating drums with
baffles, when the process is stopped; samples are moved out from the instrument, wiped-

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off dust and weighted again. The difference between the weight before and after the
process is determined as Friability and should not exceed 1%, which is considered an
ideal percentage. In some cases, where diameter of tablets is greater than 13mm, such
tablets are tested on drums 10° tilted.

Figure 4, Friability Test Apparatus

Methods:

USP provides guidelines for the friability determination of compressed, uncoated tablets.
The test procedure presented in USP is generally applicable to most compressed tablets.
Measurement of tablet friability supplements other physical strength measurements, such
as tablet crushing strength. Use a drum, with an internal diameter between 283 and 291
mm and a depth between 36 and 40 mm, of transparent synthetic polymer with polished
internal surfaces, and not subject to static buildup (see figure for a typical apparatus).
One side of the drum is removable. The tablets are tumbled at each turn of the drum by
a curved projection with an inside radius between 75.5 and 85.5 mm that extends from
the middle of the drum to the outer wall. The drum is attached to the horizontal axis of a
device that rotates at 25 ±1 rpm. Thus, at each turn the tablets roll or slide and fall onto
the drum wall or onto each other.

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Figure 5 Diagram of Friability Test Apparatus

For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets
corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, take a sample
of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately
weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times,
and remove the tablets. Remove any loose dust from the tablets as before, and accurately
weigh. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are
present in the tablet sample after tumbling, the sample fails the test. If the results are
doubtful or if the weight loss is greater than the targeted value, the test should be repeated
twice and the mean of the three tests determined. A maximum mean weight loss from the
three samples of not more than 1.0% is considered acceptable for most products. If tablet
size or shape causes irregular tumbling, adjust the drum base so that the base forms an
angle of about 10 with the bench top and the tablets no longer bind together when lying
next to each other, which prevents them from falling freely. Effervescent tablets and

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chewable tablets may have different specifications as far as friability is concerned. In the
case of hygroscopic tablets, an appropriate humidity controlled environment is required
for testing. Drums with dual scooping projections, or an apparatus with more than one
drum, for the running of multiple samples at one time, are also permitted.

Disintegration test:

In pharmaceutical industry, disintegration is an essential test performed for testing

disintegration capability of tablets and capsules etc as per pharmacopoeial standards like
USP, BP and IP etc. Each pharmacopoeia standard has its own set of standards and
specifies disintegration tests of its own.

The aim of this test is to monitor quality of different dosage forms and their performance
through evaluating the time a formulation (tablet or capsule) takes to completely
disintegrate. If disintegration time is found too high, it is considered that the tablet is highly
compressed or the capsule shell gelatin is not adhering to pharmacopoeial quality. This
test is also done to check consistency and uniformity of batches; if any kind of
inconsistency is found and the samples fail to provide adequate results, appropriate
actions can be taken on the basis of these results

Apparatus details:

The apparatus consists of a basket rack assembly, a 1000mL, low form beaker, 138 to
160 mm in height and having an inside diameter of 97 to 115 mm for the immersion fluid,
a thermostatic arrangement for heating the fluid between 35 and 39 , and a device for
raising and lowering the basket in the immersion fluid at a constant frequency rate
between 29 and 32 cycles per minute through a distance of not less than 53 mm and not
more than 57 mm. The volume of the fluid in the vessel is such that at the highest point
of the upward stroke the wire mesh remains at least 15 mm below the surface of the fluid
and descends to not less than 25 mm from the bottom of the vessel on the downward
stroke. At no time should the top of the basket rack assembly become submerged. The
time required for the upward stroke is equal to the time required for the downward stroke,
and the change in stroke direction is a smooth transition, rather than an abrupt reversal
of motion. The basketrack assembly moves vertically along its axis. There is no
appreciable horizontal motion or movement of the axis from the vertical.

Basket Rack Assembly— The basket rack assembly consists of six open-ended
transparent tubes, each 77.5 ± 2.5 mm long and having an inside diameter of 20.7 to 23
mm and a wall 1.0 to 2.8 mm thick; the tubes are held in a vertical position by two plates,

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each 88 to 92 mm in diameter and 5 to 8.5 mm in thickness, with six holes, each 22 to 26

mm in diameter, equidistant from the center of the plate and equally spaced from one
another. Attached to the under surface of the lower plate is a woven stainless steel wire
cloth, which has a plain square weave with 1.8 to 2.2mm apertures and with a wire
diameter of 0.57 to 0.66 mm. The parts of the apparatus are assembled and rigidly held
by means of three bolts passing through the two plates. A suitable means is provided to
suspend the basket rack assembly from the raising and lowering device using a point on
its axis. The design of the basket rack assembly may be varied somewhat, provided the
specifications for the glass tubes and the screen mesh size are maintained. The basket
rack assembly conforms to the dimensions found in Figure 1.

Disks— The use of disks is permitted only where specified or allowed in the monograph.
If specified in the individual monograph, each tube is provided with a cylindrical disk 9.5
± 0.15 mm thick and 20.7 ± 0.15 mm in diameter. The disk is made of a suitable
transparent plastic material having a specific gravity of between 1.18 and 1.20. Five
parallel 2 ± 0.1 mm holes extend between the ends of the cylinder. One of the holes is
centered on the cylindrical axis. The other holes are centered 6 ± 0.2 mm from the axis
on imaginary lines perpendicular to the axis and parallel to each other. Four identical
trapezoidalshaped planes are cut into the wall of the cylinder, nearly perpendicular to the
ends of the cylinder. The trapezoidal shape is symmetrical; its parallel sides coincide with
the ends of the cylinder and are parallel to an imaginary line connecting the centers of
two adjacent holes 6 mm from the cylindrical axis. The parallel side of the trapezoid on
the bottom of the cylinder has a length of 1.6 ± 0.1 mm, and its bottom edges lie at a
depth of 1.6 ± 0.1 mm from the cylinder's circumference. The parallel side of the trapezoid
on the top of the cylinder has a length of 9.4 ± 0.2 mm, and its center lies at a depth of
2.6 ± 0.1 mm from the cylinder's circumference. All surfaces of the disk are smooth. If the
use of disks is specified in the individual monograph , add a disk to each tube, and operate
the apparatus as directed under Procedure. The disks conform to dimensions found in
Figure 1

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Figure 6, Diagram of Disintegration test apparatus

Procedure
Uncoated Tablets — Place 1 dosage unit in each of the six tubes of the basket and, if
prescribed, add a disk. Operate the apparatus, using water or the specified medium as
the immersion fluid, maintained at 37 ± 2 . At the end of the time limit specified in the
monograph, lift the basket from the fluid, and observe the tablets: all of the tablets have
disintegrated completely. If 1 or 2 tablets fail to disintegrate completely, repeat the test on
12 additional tablets. The requirement is met if not fewer than 16 of the total of 18 tablets
tested are disintegrated.

Plain Coated Tablets — Apply the test for Uncoated Tablets, operating the apparatus
for the time specified in the individual monograph.

Delayed Release (Enteric Coated) Tablets— Place 1 tablet in each of the six tubes of
the basket and, if the tablet has a soluble external sugar coating, immerse the basket in
water at room temperature for 5 minutes. Then operate the apparatus using simulated
gastric fluid TS maintained at 37 ± 2 as the immersion fluid. After 1 hour of operation in

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simulated gastric fluid TS, lift the basket from the fluid, and observe the tablets: the tablets
show no evidence of disintegration, cracking, or softening. Operate the apparatus, using
simulated intestinal fluid TS maintained at 37 ± 2 as the immersion fluid, for the time
specified in the monograph. Lift the basket from the fluid, and observe the tablets: all of
the tablets disintegrate completely. If 1 or 2 tablets fail to disintegrate completely, repeat
the test on 12 additional tablets: not fewer than 16 of the total of 18 tablets tested
disintegrate completely. Buccal Tablets— Apply the test for Uncoated Tablets. After 4
hours, lift the basket from the fluid, and observe the tablets: all of the tablets have
disintegrated. If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12
additional tablets: not fewer than 16 of the total of 18 tablets tested disintegrate
completely. Sublingual Tablets— Apply the test for Uncoated Tablets. At the end of the
time limit specified in the individual monograph: all of the tablets have disintegrated. If 1
or 2 tablets fail to disintegrate completely, repeat the test on 12 additional tablets: not
fewer than 16 of the total of 18 tablets tested disintegrate completely.

Disintegration Media
water,
Simulated gastric fluid (pH = 1.2 HCl), or Simulated intestinal fluid (pH = 7.5, KH2PO4
(phosphate buffer) + pancreatic enzyme + NaOH)

Figure 7, Disintegration test apparatus

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Disintegration Testing Conditions and Interpretation

Sr. no. Type of tablets Medium Temperature limit

1 Compressed uncoated Water 37 ± 20C 15 minutes or
as per
individual
monograph
2 Sugar coated 0.1 N HCL 37 ± 2 0C 60 minutes or
If 1 or 2 tablets fail as per
individual
monograph
3 Film coated water 37 ± 20C 30 minutes or
as per
individual
monograph
4 Enteric coated 0.1 N HCL & 37 ± 20C 1 hr or as per
Phosphate individual
buffer pH 6.8 monograph
5 Dispersible/ water 25 ± 20C LST < 3
Effervescent minutes or as
per individual
monograph

Dissolution Test
Dissolution is performed to check the percentage release from the dosage forms. i.e.
Tablet.

Tablet breaks down into small particles which offers a greater surface area to the
dissolving media.

Disintegration test does not give assurance that particles will release drug in solution at
an appropriate rate, that’s why dissolution tests & its specifications developed for all tablet
products.

Mechanism:
Dissolution is mass transfer process.
Dissolution is mainly depend on aqueous solubility of drug.
It is process in which solid mass transfer in liquid medium.
Dissolution based on four process – 1. wetting 2. Solubility 3. Swelling 4. Diffusion.

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Particle size, shape, surface area is important factor can affect the rate of dissolution of
drug.
The aqueous solubility is increases, increases rate of dissolution drug.

Figure 8, Mechanism of Dissolution

Factor affecting dissolution rate

Physicochemical Properties of Drug
Drug Product Formulation Factors
Processing Factors
Factors Relating Dissolution Apparatus
Factors Relating Dissolution Test Parameters

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Dissolution test apparatus

USP apparatus
1. Apparatus 1 (rotating basket)

2. Apparatus 2 (paddle assembly)

USP Dissolution apparatus I (Basket method)

A single tablet is placed in a small wire mesh basket attached to the bottom of the shaft
connected to a variable speed motor. The basket is immersed in a dissolution medium
(as specified in monograph) contained in a 1000 ml flask. The flask is cylindrical with a
hemispherical bottom. The flask is maintained at 37 ± 0.50C by a constant temperature
bath. The motor is adjusted to turn at the specified speed and sample of the fluid are
withdrawn at intervals to determine the amount of drug in solutions.

Figure 9A, Dissolution test apparatus, apparatus 1 (rotating basket)

Figure 9B, Dissolution test apparatus, apparatus 1 (rotating basket)

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USP Dissolution apparatus II (Paddle method)

It is same as apparatus-1, except the basket is replaced by a paddle. The dosage form is
allowed to sink to the bottom of the flask before stirring. For dissolution test U.S.P.
specifies the dissolution test medium and volume, type of apparatus to be used, rpm of
the shaft, time limit of the test and assay procedure for. The test tolerance is expressed
as a % of the labeled amount of drug dissolved in the time limit.

Figure 10A, Dissolution test apparatus, apparatus Apparatus 2 (paddle assembly)

Figure 10B, Dissolution test apparatus, apparatus Apparatus 2 (paddle assembly)

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Dissolution Testing and Interpretation USP Standards

Sr.no. Quantity Number of Acceptance

Stage/level tablets tested criteria
1 S1 6 Each unit is < D* +
5 percent**
2 S2 6 Average of 12
units (S1 +S2) is
equal to or greater
than (> )D, and no
unit is less than D -
15 percent**
3 S3 12 Average of 24
units (S1+S2+S3)
is equal to or
greater than (> )D,
not more than 2
units are less than
d-15 percent** and
no unit is less than
d-25 percent**

Dosage from conducted dissolution study

Immediate release tablet (conventional tablet)
1. Dissolution apparatus – Type 1 and Type 2 (USP)
2. Temperature - 37±0.5˚C
3. Time – 30 min
4. Time of interval – 5, 10, 15, 20, 25, 30.
5. Media – PH 1.2 Acidic Buffer, PH 4.5 Acetate buffer, PH 5.8 Phosphate buffer.
(depending upon tablet)
6. Rpm – 75 -100 rpm
7. Volume – 900 ml

Procedure: The tablet was added into cylindrical vessel containing 1000 ml dissolution
media having rpm 75 and tem.37±0.5˚C. Dissolution of tablet was conducted 30 min, in
5 min. of interval, after 5 min 5 mL sample was removed and appropriate quantity of

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sample take absorbance by using U.V. spectroscopy technique and determine rate of
dissolution of tablet.

Sustained release tablet

1. Dissolution apparatus – Type 2 (USP)
2. Temperature - 37±0.5˚C
3. Time – 7 hrs
4. Media – PH 1.2 Acidic Buffer, PH 6.8 Phosphate buffer.
5. Rpm – 75 – 100.
6. Volume – 900 ml.

Procedure - The tablet was added into cylindrical vessel containing 1000 ml PH 1.2
Acidic media having rpm 75 for next two hours and tem. 37±0.5˚C. Dissolution media was
changes tablet was added in to PH 6.8 Phosphate buffer for next five hour for 1 hr. of
interval. After 1 hr. 5 mL sample was removed and appropriate quantity of sample take
absorbance by using U.V. spectroscopy technique and determine rate of dissolution of
tablet.

Content Uniformity:
Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if
9 of the 10 tablets must contain not less than 85 % and not more than 115 % of the
labeled drug content and the 10th tablet may not contain less than 75 % and more
than125 % of the labeled content. If these conditions are not met, remaining 20 tablet
assayed individually and none may fall outside of the 85 to 115 % range.

Evaluation of Precompressional Characteristics of tablets or Rheological

Characteristics of granules

Particle Size & Shape Determination

Size affects the average weight of tablet, Disintegration Time, weight variation, friability,
flow ability & drying rate.
The size & shape depends upon processing requirements & during granulation.
The methods for determining size & shape are

1. Sieving
2. Sedimentation rate.
3. Microscopy (SEM)

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Angle of repose – It is measured by two methods

Static angle of repose
Dynamic angle of repose

Equation is, tan θ = h/r.

Where, θ - angle of repose, h – height of pile, r – radius of pile.

Acceptance limits of angle of repose

Sr. no. Angle of repose Type of flow
(o)
1 < 25 Excellent
2 25-30 Good
3 30-40 passable
4 > 40 Poor

Hausner's Ratio

Hausner’s ratio was related to interparticulate friction and as such could be used to
predict powder flow characteristics.

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It shows that the Powder with low particular friction such as coarse sphere had ration of
approximaty 1.2, whereas more as cohesiveness less free flowing powders such as flax
have Hausner’s ratio greater than 1.6

Formula

Hausner’s ratio= Tapped density/ Bulk density

Compressibility Index
It is directly related to the relative flow rate cohesiveness & particle size.
It is simple fast & popular method of presiding powder flow characters.

It can be obtained from bulk density measurements is the % Compressibility index (C).
% Compressibility index = Tapped density - Bulk density / Tapped density X 100.
OR
I = (1 – V/ Vo) x 100
Where,
I – % Compressibility index,
V – Volume occupied by powder/ granules after tapping, Vo - volume of powder/granules

before tapping

Acceptance limit Compressibility index

Sr. no. % Compressibility Type of flow

index
1 5-15 Excellent
2 12-16 Very good
3 18-21 Good
4 23-25 Passable
5 33-38 Poor
6 > 40 Very poor

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