QUALITY CONTROL OF SOLID

DOSAGE
FORM
Dr. Nariman Shahid
Introduction
• QC is strictly observed in order to ensure that the product is not only
meeting the requisite specifications but also reproducible in terms of
quality, hence therapeutically effective.
• Solid dosage forms are:
• - Tablets
• - Capsules
• - Powders
• - Granules
Quality Control of Tablets

• INTRODUCTION
• Tablets are solid dosage forms intended for oral administration containing
unit dose of one or more medicaments.
• Tablets are prepared by compressing uniform volume of particles through:
- Direct Compression
- Wet Granulation
- Dry Granulation. Also known as:
▪ Slugging and double compression.
• They are swallowed whole or dissolved/dispersed in water before intake.
.
Quality control tests for tablets
• Quality control tests for tablets include;
• Physical tests Chemical tests
• Tablet Hardness Content uniformity
• Tablet Thickness and diameter Assay
• Friability Dissolution test
• Disintegration test
• Weight variation
Unofficial tests
1. Hardness
• Hardness related to solubility, proper hardness for tablets ensures that tablet with
stand the shock of handling, packing and shipping.
Common hardness testers;
• Strong-cobb
• Stokes monsanto
• Eureka
• Pfizer units
Mechanical tester
• Hardness is normally tested by mechanical tester now a days with automatic operation. Mechanical
tester measures resistance to crushing of tablets.
• Force is applied by a beam. One end of beam is attached to pivot controlled mechanically by a motor.
The other end rests on tablets. Motor moves the beam which applies force on tablets. When the tablet
breaks a micro switch stops the motor. Mechanical strength is shown in the digital indicator.
• Hardness specifications
• Acceptable range is 5 – 10 Kg/ cm2. Sometimes the scale is in Newton (1 Newton = 9.8 kg).
.
Monsanto hardness tester:
• Hold one tablet between the
two faces provided by
pushing forward the
movable face inside by
turning the plunger
clockwise.
• Turn the screw knob slowly
till the tablet breaks. The
pressure indicated on the
dial is in Kilogram per sq.
cm.
.
2. Tablet thickness and diameter
• Checking of thickness and diameter is usually an in process quality control check during
production. Dimensional specifications of tablets are very important because of many reasons;
 Packaging requirements
 Patient compliance
 Thickness is often related to tablet’s hardness’
 Directly effect to assay results
• The apparatus used for this purpose are;
 Micrometer screw gauge
 Vernier caliper
• Now a days digital micrometers are available.
Thickness specification
• Limits on thickness of tablet weight;
 Thickness of tablet varies from 2 – 4 mm depending upon diameter of tablet.
 A deviation of ± 5% from stated diameter is allowed except that for exceeding 12.5 mm.
 For 12.5 mm or above deviation is ± 3%
..
.3. Friability
• (Ph. Eur. Method 2.9.7)
• Friction and shock during tableting can cause tablet to chip, cap and break.
Loss of weight due to abrasion of friction is the measure of tablet’s friability.
• The apparatus used for the purpose is;
 Roche Friabilator
• It consist of hard plastic cylinder of 6 inch radius. Motor which rotates
cylinder at constant speed.
• Use a drum, with an internal diameter between 283-291 mm and a depth
between 36-40 mm, of transparent synthetic polymer with polished internal
surfaces, and subject to minimum static build-up (see Figure 2.9.7.-1.).
.• 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 75.5-85.5 mm
that extends from the middle of the drum to the outer wall. The outer diameter
of the central ring is between 24.5-25.5 mm. The drum is attached to the
horizontal axis of a device that rotates at 25 ± 1 r/min. Thus, at each turn the
tablets roll or slide and fall onto the drum wall or onto each other.
• Effervescent tablets and chewable tablets may have different specifications
as far as friability is concerned. In the case of hygroscopic tablets, a humidity-
controlled environment is required for testing.
• A drum with dual scooping projections, or apparatus with more than one
drum, for the running of multiple samples at one time, are also permitted.
• For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets
.
corresponding as near as possible to 6.5 g. For tablets with a unit mass of more than 650 mg,
take a sample of 10 whole tablets. The tablets are 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 difficult to interpret
or if the weight loss is greater than the targeted value, the test is repeated twice and the mean of
the 3 tests determined. A maximum loss of mass (obtained from a single test or from the mean
of 3 tests) not greater than 1.0 per cent is considered acceptable for most products.
• Procedure for friability testing
1. 8 to 10 tablets are taken on random basis.
2. Cumulative weight is recorded.
3. Tablets are rotated in friabilator for 4 minutes (100 revolutions) at constant speed of 25rpm.
4. Tablets are weighed and compared to original weight.
5. Value of friability (or weight loss) is expressed as percent w/w.
• Specifications of friability
• The USP states that the friability should be 0.8 – 1%.
.
4. Weight variation test
• Compression weight, Actual weight of tablet is determined by the diameter
of the die and weight adjustment cam on tablet compression machine.
• Weight control on tablet is continuously checked and adjusted during
compression of whole batch. It is normally done on uncoated tablets.
• Procedure for weight variation
1. Weight individually 20 whole tablets.
2. Calculate average weight.
3. Weight of no more than two tablets differs from the average weight by
more than the percentage given.
4. No tablet differ by more than double the percentage given.
.
• Weight variation specifications
• By USP
Avg. weight of tablet Percentage difference
130 mg or less ± 10.0 %
For 130 mg to 324 mg ± 7.5 %
More than 324 mg ± 5.0 %
By BP;
Avg. weight of tablet Percentage difference
80 mg or less ± 10.0 %
> 80 mg to < 250 mg ± 7.5 %
250 mg or more ± 5.0 %
Official tests
1. Disintegration
• It is the time required for the tablet to break into particles, the disintegration test is
a measure only to the time required under a given set of conditions for a group of
tablets to disintegrate into particles.
• Disintegration test
• Complete disintegration is defined as that state in which any residue of the tablet,
except fragments of insoluble coating remaining on the screen of the test apparatus,
soft mass having no firm core remains.
• It is done because of following reasons;
 To ensure product uniformity
 Attempts are made to simulate in-vivo conditions.
 Actually test does not correlate with physiological conditions.
 It is done as a process control.
• Disintegration apparatus;
.
1.
2.
Basket rack assembly
Suitable vessel of immersion fluid
3. Immersion fluid
4. Thermostat
5. A motoring device for raising and lowering the basket assembly in fluid
6. Discs
Basket rack assembly
• It consist of six open ended glass tubes each 7.5 ± 0.25 cm long and inside diameter approx. 21.5 mm and wall thickness is
approx. 2mm. Tubes are held vertically with the help of two plastic plates each about 9 cm in diameter and 6 mm in thickness.
Plastic plates consist of 6 holes each about 24 mm diameter.
• 10 mesh (sieve opening 2 mm) and gauge woven stainless steel wire cloth is attached with screws to the under surface of lower
plate. Glass tubes and upper plastic plates are screwed in position by means of stainless steel plate. Central shaft 8 cm in length
upper end of which terminates in an eye through which a string or wire may be inserted.
• Design of plastic assembly may vary between manufacturers but must comply with specifications.
Discs
• The decision to include plastic discs is based on the specific gravity of the tablets to take care of floating tablets. Slotted and
perforated discs of 9.5 ± 0.15 mm thickness and 20.7 ± 0.15 mm in diameter.
• They are made up of transparent material, specific gravity between 1.18 and 1.20.
• All surfaces of the discs are smooth. Five 2 mm holes are drilled perpendicular to the cylindrical axis.
• Thermostat
• For heating the fluid between 35oC to 39oC.

.
• Device for lowering and raising basket rack assembly
• Up and down cycles perforated at rate between 28 and 32 cycles per minute through a distance of not less than 5 cm and not more than 6
cm.
• Volume of fluid in vessel is adjusted as such that the highest point of upward stoke the wire mesh remains 2.5 cm from the bottom of
vessel.
• Time require for upward stoke should be equal to time require for downward stoke. The change in stoke direction should be smooth.
• Immersion fluid
1. Water: use distilled water
2. Hydrochloric acid: use ACS reagent code
3. Sodium chloride: use ACS reagent code
4. Pepsin
5. Potassium phosphate, monobasic: use ACS reagent code
6. Pancreatin: a USP grade
7. Hydrochloride solution (0.1M): Dilute 8.5 ml of HCl to 1000 ml with water, or dilute a commercial
volumetric solution with water to obtain a final concentration of 0.1M.
8. Sodium hydroxide (0.2M): Use ACS reagent grade. Dissolve 8g of sodium hydroxide in and dilute to 1000 ml
with carbon dioxide free water, or dilute a commercial volumetric solution with carbon dioxide free water to
give a final concentration of 0.2M.
9. Simulated gastric fluid: Dissolve 2.0g of sodium chloride and 3.2 g of pepsin in 500 ml of water and 7.0 ml of
HCl and dilute to 1000 ml with water. The pH is about 1.2
10. Simulated intestinal fluid: dissolve 68g of potassium phosphate monobasic in 250 ml in water. Add 10.0g of
pancreatin mix and adjust the pH of the resulting solution to 7.5 ± 0.1 with NaOH (0.2M) dilute with water to
1000 ml.
Uncoated and plain coated tablets(B.P)
1. Assemble the apparatus when the device for arising and lowering the basket rack assembly is at rest
and its cylinder in the extreme down position.
2. With 2.5 L or appropriate amount of water in the cylindrical jar, adjust the apparatus until the level of
fluid in the jar coincides approximately with the mid line of the upper plastic plate.
3. Maintain the temperature of the fluid at 37 ± 2oC by suitable means.
4. Remove the basket rack assembly form the water and disassemble.
5. Select at random six tablets from the sample and place one in each of the tubes of the basket rack
assembly.
6. Place a plastic disk on each tablet according to the specific gravity of tablet.
7. Reinsert the assembly in the water and set the machine in motion.
8. The plastic discs should travel up and down freely exerting a gentle rubbing action on each tablet.
After 15 minutes remove the basket rack assembly from the water.
9. Uncoated tablets pass the test if each of the six uncoated tablets disintegrates in not more than 15
minutes.
10.If 1 and 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets; not less than
16 of the total of 18 tablets tested disintegrate completely.
11.Plain coated tablets pass the test if each of the six plain coated tablets disintegrate in not more than 60
minutes. If any of the tablets has not disintegrated at the end of 60 minutes, repeat the test of further
six plain coated tablets replacing the water in the cylindrical jar with HCl (0.1M). The tablets pass the
test if each of the six tablets disintegrates within 60 minutes in the acid medium.
Enteric coated tablets
1. Assemble the apparatus as described using 2.5 L of simulated gastric fluid in place of
water.
2. Remove the basket rack assembly from the simulated fluid and disassemble.
3. Select at random six tablets from the sample and place one in each of the tubes of the
basket rack assembly.
4. Place a plunger in each tube as specified (omitting the plastic disc).
5. Insert the assembly in the simulated gastric fluid and set the machine in motion.
6. At the end of 60 minutes of operation, remove the basket rack assembly from the fluid
and gently rinse with water.
7. Enteric coated tablets fail the test if any of tablet show distant evidence of disintegration.
8. Replace the simulated gastric fluid in the jar with 2.5 L of simulated intestinal fluid.
9. Remove the plungers, place a plastic disc on each tablet, and re-insert the plunger
10.Continue the test by setting the machine in motion.
11.After 30 minutes remove the basket rack assembly from the fluid.
12.Enteric coated tablets pass the test if each of the six tablets disintegrates in not more than
30 minutes in the simulated intestinal fluid.
• If 1 and 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets; not
less than 16 of the total of 18 tablets tested should disintegrate completely.
.
• Buccal tablets
1. Apply the test for uncoated tablets, but omit the use of disc.
2. After 4 hours, lift the basket from fluid and observe the tablets all of the tablets
should be disintegrated.
3. If 1 and 2 tablets fail to disintegrate completely repeat the test on 12 additional
tablets; not less than 16 of the total of 18 tablets tested disintegrate completely.
• Sublingual tablets
1. Apply the test for uncoated tablets, but omit the use of disc.
2. Observe the tablets within the time limit specified in individual monograph; all
the tablets have disintegrated.
3. If 1 and 2 tablets fail to disintegrate completely repeat the test on 12 additional
tablets; not less than 16 of the total of 18 tablets tested disintegrate completely.
2. Dissolution
• It is a process by which solid enters into solution. It is one of the most important
QC test. Dissolution test represents in-vivo drug dissolution however far from being
understood properly. Therapeutic deficiency cannot rely on dissolution test alone. In
considering drug absorption one must consider;
 Total dose required
 Water and/or oil solubility
 pKa of drug
• Dissolution is directly related to solubility. Drugs that have solubility greater than
1% (1 w/v) are generally no problem. It is applied primarily to those drugs which
have low solubility.
• Since drug absorption and physiological availability are largely dependent upon
having the drug in dissolve state suitable dissolution characteristic are an important
property of QC. Usually method of dissolution and specifications are given in
individual monographs.
.• Dosage forms to be tested
 Immediate release dosage forms
 Controlled release dosage forms
 Transdermal systems
 Implants
• Official dissolution apparatuses
1. Rotating basket
2. Paddle
3. Reciprocating cylinder
4. Flow through cell
5. Paddle over disk
6. Rotating cylinder
7. Reciprocating holder
• Selection of apparatus
.
• The choice of the apparatus is based on one’s knowledge regarding the
formulation design, dosage form and performance. Besides the selection of an
adequate dissolution apparatus adequate test conditions are crucial for all purposes.
• It depends upon one’s intention;
• Quality control
 Examining batch homogeneity
 Examining batch to batch conformity
 Examining stability
• Research and development
 Examining drug release behavior in preformulations
 In-vitro simulation of the GIT passage
•
Apparatus 1 – Basket
• It is useful for capsules, bead, delayed release/ enteric coated dosage forms, floating dosage forms,
surfactants in media. The standard volume is 900/ 1000 ml. 1, 2 and 4 liter vessels.
• It consist of following parts;
 1000 ml vessel
 A variable speed vessel
 Cylindrical stainless steel basket
 Water bath (whole assembly is immersed in it for keeping temperature constant at 37 ± 0.5oC
throughout the test).
• Vessel: it is made up of glass or any other inert transparent material. It is 1000 ml in volume
capacity. It has slightly concave bottom with 16cm height (internal height) and 10cm inside diameter.
The slides are flanged near top end to accept a fitted cover. Cover has four ports one of which is
cantered for motor shaft. One of the other port is for thermometer. Other two ports are for sample
removal for analysis and one for addition/ replacement of dissolution medium.
• Variable speed motor: the shaft of the motor is placed in central port to facilitate the rotation of
basket assembly smoothly. Shaft in 6 mm in diameter and 30 cm in length. Motor speed is varied
between 25 rpm – 200 rpm and to be maintained as described in individual monograph with ± 5%.
Motor is suspended in such a way that it may be raised or lowered to position the basket.
• Basket assembly: basket assembly consist of two parts;
.
- Part 1: it is attached to the shaft. It is solid metal. It is fitted with three spring clips that
allows removal of lower parts or basket proper to admit test sample.
- Part 2: it is detachable part consist of fabricated welded seam. It has 40 mesh stainless
steel cloth formed into cylinder shaped. Its height is 3.66 cm and diameter is 2.5cm.
• Basket also contain metal rim sheet at top. A gold plated basket coating 0.0001 inch
(2.5µm) thick is recommended for tests carried out in dilute acid medium.
Advantages
 It has a breadth of experience (more than 200 monographs)
 Full pH change during the tests
 It can be easily automated which is important for routine investigations.
Disadvantages
 Disintegration – dissolution interaction
 Hydrodermic dead zone under the basket degassing is particularly important.
 Limited volume sink conditions for poorly soluble drugs.
Apparatus 2 – Paddle
• It is useful for tablets, capsules, beads, delayed release dosage forms, enteric coated
dosage forms. Its standard volume is 900/ 1000ml. It is normally the method of first choice.
• Advantages
 It is easy to use
 It is robust
 It is easily adapted to apparatus 5
 It has breadth of experience
 pH alteration is possible
 It can be easily automated which is important for routine investigations.
• Disadvantages
 pH/ media change is often difficult
 Limited volume, sink conditions for poorly soluble drugs
 Hydrodynamics are complex, they vary with site of the dosage form in the vessel
(sticking, floating) and therefore may significantly affect drug dissolution.
 Sinkers for floating dosage form.
Apparatus 3 – Reciprocating cylinder
• It is useful for tablets, beads, and controlled release dosage forms. Its
standard volume is 200 – 250 ml per station.
• Advantages
 It is easy to change pH.
 Huge pH profiles
 Hydrodynamics can be directly influenced by varying the dip rate.
• Disadvantages
 It has small volume
 It has little experience and It provides limited data
Apparatus 4 – flow through cell
• It is used for low solubility drugs, microparticulates, implants, suppositories, and
controlled release formulations. It has variations; open or closed system.
• Advantages
 It is easy to change pH and media.
 pH profile is possible.
 No sink conditions
 It has different modes; open and closed system.
• Disadvantage
 Deaeration is necessary
 High volume of media is required
 It is labor intensive process
•
Apparatus 5 – Paddle over disk
.
• The method is useful for the transdermal patches. The standard volume is 900 ml.
• Advantages
 Standard apparatus (paddle) can be used, only add a stainless steel disk assembly.
• Disadvantages
 Disk assembly restricts patch size

Apparatus 6 – Rotating cylinder

• Most probably will be removed from USP.

Apparatus 7 – Reciprocating holder

• Most probably will be removed from USP.
Dissolution testing for various dosage forms
• Solid dosage forms include;
1) Immediate release dosage forms (tablets and capsules)
2) Delayed release dosage forms
3) Dosage forms for oral cavity
i) Buccal/ sublingual tablets
ii)Medicated chewing gums
4) Suppositories
5) Semisolid dosage forms
6) Soft gelatin capsules
Dissolution testing for immediate release (IR)
dosage forms
• An immediate release dosage form is designed to deliver the drug rapidly into the
systemic circulation. Therefore, the dissolution may be the rate limiting step for the
absorption. Generally dissolution if IR dosage forms are being conducted using apparatuses
of basket, paddle, reciprocating cylinder and flow through cell. The apparatus 1 and 2 are
most commonly used.
• USP uses basket, paddle, EP uses paddle over basket and flow through cell apparatuses
for solid dosage forms of tablets & capsules.
• The dissolution test is carried out at 37oC ± 0.5oC. In general when basket apparatus is
used rotation speed is 100 rpm with 40 mesh screen of the basket is used. Other mesh sizes
may also be used if supported by necessary data documentation. It is generally used for
capsules and floating type dosage forms or to those which tend to disintegrate slowly. For
floating type of dosage forms sinker may be used to prevent the floating of capsules.
• Paddle apparatus is used for tablets. Operating speed of 50rpm is used in general.
Procedure
Method I
1. Unless otherwise directed in the individual monograph, place 900ml fluid in the dissolution
vessel.
2. Vessel should previously be immersed in water bath and allow dissolution temperature to come at
37oC ± 0.5oC.
3. Place one tablet or one capsule in the basket so that there is distance of 2.0 ± 0.2 cm between
basket and bottom of vessel.
4. Rotate the basket at a rate specified in the monograph.
5. Withdraw sample at the time indicated and analyze them by procedure described in the individual
monograph.
6. The dissolution testing is done in three stages of S1, S2, and S3.
7. In stage 1(S1), 6 units are taken and the amount of drug from each unit should not be less than Q
+ 5% where Q is the maximum amount of drug dissolved i.e. active ingredient specified in
individual monograph.
8. Failure of first stage (if one or two tablets fail to comply) compensate to conductance of second
stage S2 where additional 6 units are tested.
9. The avg. of 12 units in two stages should be equal to or greater than Q and no unit should be less
than Q – 15%.
10.Failure of stage 2 leads to conductance of stage S3 where additional 12 units are tested and the
avg. of total units of three stages S1, S2 and S3 should be greater than or equal to Q and no two
units should be less than Q – 15% and none should be less than Q – 25%.
Note: Unless otherwise specified maintain the volume in vessel constant by adding a volume of
dissolution medium equivalent to that removed for sampling.

Stage Number tested Acceptance criteria

S1 6 Amount of drug released from each unit is not less
than Q + 5%.
S2 6 Avg. of S1+S2 (12 units) is equal to or greater than
Q and no unit is less than Q -15%.

S3 12 Avg. of S1+S2+S3 (24 units) is equal to or greater

than Q , not more than 2 units are less than Q – 15%
and no unit is less than Q - 25%.
.• Chewable tablets
• USP insisted the use of apparatus 2 for dissolution excepting ampicillin where apparatus 1
is recommended and carbamazepine where apparatus 2 and 3 are used.
• The design of apparatus should consist of a mechanical breakage of tablet prior to
dissolution.
• Buccal/ sublingual tablets
• Initially USP stated the use of disintegration apparatus for the ergotamine category
sublingual products. Later modified USP apparatus 3 with 20 strokes/ min was used for
hydrocortisone mucoadhesive tablets to mimic the low dissolution volume of in-vivo.
• Later another system continuous flow through filtration cell with dip tube for filtration. 10
ml of fluid is pumped to give a short residence time of 8 minutes.
• Chewing gums
• USP has not recommended any apparatus for dissolution testing of chewing gums, but EP
has emphasized on the use of 3 piston apparatus that chews the gum at a rate of 60 cycles/
min in dissolution medium of pH 6.0 at 37oC.
3. Content uniformity
• The content uniformity test is done to ensure that each dosage form contains the exact
stated amount of drug within a batch. Mainly it is used for testing the consistency of;
 Bulk powders before or after compression
 Liquid orals before filling
 Also during filling of powders into capsules or liquids into vials and ampules
 Amount of API within individual unit of tablet and capsule
• Only when the ingredient of the tablet granulation are homogenous, tablet weight test as
described earlier can be considered as a measure of drug content.
• Routinely the assay of the drug content in tablets involve the grinding of tablet of large
sample of (20) tablets followed by the analysis of an aliquot. Normally testing is confirmed
by performing specific assay to determine the content of drug material contained in
particular dosage form.
• Results obtained are expressed as percentage of active ingredient in the tablet or on
individual tablet basis. Different pharmacopoeias describe the procedure of content
uniformity test and give their specifications.
.• Stage 1: Take 10 units randomly and perform the assay. It passes the test if relative standard
• Content uniformity test USP

deviation is less than 6% and no value is outside 85 – 115%. Fails the tests if one or more values are
out of 75 – 125%.
• Stage 2: Take 20 more units and perform the assay. Passes the test if RSD of all 20 tablets is less
than 7.8%, not more than one value is outside 85 – 115 % and no value is outside 75 – 125% or else,
the batch fails the test.
• Content uniformity test BP
• Test A: The test is applicable for tablets, powders for parenteral use and suspensions for injection.
1. Select 10 units at random and perform the assay. Passes the test if each individual unit is between
85 – 115% of the average content.
2. Fails the test if more than one individual unit is outside these limits or if even one unit is outside
the limit of 75 – 125% of the avg. content. But if one unit is outside the limit of 85 – 115 % and
within 75 – 125 % then take another 20 units at random and perform the assay.
3. The lot passes the test if not more than 1 unit of 30 units is outside 85 – 115% and not even one
unit is outside the limit of 75 – 125% of the avg. content.
.• Test B: The test is used for capsules, powders, other than parenteral use; granules,
suppositories and pessaries.
1. Select 10 units at random and perform the assay. Passes the test if not more than 1
individual unit is outside the limits of 85 – 115% and none is outside the limits of 75 –
125%of the labelled content.
2. The batch fails the test if more than 3 units are outside the limit of 85 – 115% or if one or
more units are outside the limits of 75 – 125% of the labelled content.
3. If 2 or 3 units are outside the limits of 85 – 115% but within the limits of 75 – 125% then
select another 20 units at random.
4. The batch complies the test when not more than 3 units out of these 30 units are outside
the limits of 85 – 115% and not even one unit is outside the limits of 75 – 125% of the
labelled content.
• Test C: The test is applicable to only transdermal patches.
1. The preparation passes test only if the avg. content of 10 units is between 90 – 110% and
if the content of each unit is between 75 – 125% of the avg. content.
Chemical assay of tablets
• Routinely the assay of the drug content in tablets involve the grinding of tablet of large
sample of (20) tablets followed by the analysis of an aliquot, representing the certain
amount of drug normally in a single unit.
• Analysis is performed by the methods prescribed in the individual monographs. Results
obtained are expressed in percentage of the active ingredient in the tablet or unit dose
compared with limits in the monograph of the drug.
• Common assay procedure involves;
 Titrimetric analysis
 Spectrophotometric methods
 UV spectroscopy
 HPLC
 Biological assay
 Microbial assay
.i.
• Tests for coated tablets
Water vapor permeability
ii. Film tensile strength
iii. Coted tablets evaluations
• Adhesion test with tensile strength tester
• It measure the force required to peel the film off from the tablet surface.
• Diametral crushing strength of coated tablets
• Tablets hardness testers are used. This test gives information on the relative increase in
crushing strength provided by the film and the contribution made by changes in the film
composition.
• Temperature and humidity may cause film defects, hence studies are to be carried out.
• Quantification of film roughness, hardness and color uniformity
• Visual inspection or instruments are used. Resistance of coated tablets on a white sheet of
paper. Resilient films remain intact and no color is transferred to the paper, very soft
coatings are readily “erased” from the tablet surface to the paper.
Quality control of Capsules

Quality control tests for capsules includes;

 Weight variation
 Content uniformity
 Disintegration
 Dissolution
 Chemical or biological assay
Disintegration testing
• Special type of basket rack assembly is used. The apparatus consisting of;
• A glass tube 80 – 100 mm long with internal diameter of about 28mm and
external diameter of 30 – 31 mm. At the bottom of the tube rust proof wire
gauze is attached to form a basket. Wire gauze is fitted to the tube in such a
manner that the overall diameter of the basket in not materially increased.
• A glass cylinder with a flat base and an internal diameter of about 45mm
used for disintegration media. Cylinder contains water media not less than 15
cm deep, maintained at the temperature 37 ± 2oC by suitable means.
• Basket is raised and lowered repeatedly in a uniform manner so that at
highest position, the gauze breaks the surface of water and at lowest position
the upper rim of basket cylinder just remains clear of water. Guiding disk made
up of suitable material and lowering and raising device are used.
.
• Method BP
1. Place five capsules in the basket
2. Raise and lower the basket in such a manner that complete up and down
movement is repeated thirty times per minute.
3. Capsules are disintegrated when no particle of any solid content remains above
the gauze which would not readily pass through it.
4. Time required for capsules to disintegrate is not more than 15 minutes unless
otherwise stated in individual monograph.
5. If capsules fail the disintegration test because of aggregation, further five
capsules may be tested individually.
6. The longest time taken by one of the five capsules is the disintegration time.
.
• Method USP
• According to USP disintegration test is usually not required for capsules unless have been treated
to resist solution in gastric fluid (enteric coated). In this case they must meet the requirements of
disintegration test of enteric coated tablet i.e.
1. Assemble the apparatus as described using 2.5 L of simulated gastric fluid in place of water.
2. Remove the basket rack assembly from the simulated fluid and disassemble.
3. Select at random six capsules from the sample and place one in each of the tubes of the basket
rack assembly.
4. Place a guided disc.
5. Insert the assembly in the simulated gastric fluid and set the machine in motion.
6. At the end of 60 minutes of operation, remove the basket rack assembly from the fluid and gently
rinse with water.
7. Enteric coated capsules fail the test if any of the capsule show distant evidence of disintegration.
8. Replace the simulated gastric fluid in the jar with 2.5 L of simulated intestinal fluid.
9. Reinsert the guided disc.
10.Continue the test by setting the machine in motion for 60 minutes.
11.After 30 minutes remove the basket rack assembly from the fluid.
12.Enteric coated tablets pass the test if each of the six tablets disintegrates in not more than 30
minutes in the simulated intestinal fluid.
Weight variation test for capsules
• There are two methods for testing uniformity of weight of capsules;
• Method A
• Method A is for capsules with dry content.
1. Weigh a capsule, open it without loss of shell material, remove the contents and
weigh all parts of shell.
2. The difference between the weights represents the weight of contents of capsule.
3. Repeat the operation with further 19 capsules (total 20).
4. Capsules pass the test if not more than 2 capsules deviate from the mean weight
by more than percentage given in table.
5. For one or two capsules (which are outside above given range) the weight of the
content should not be more than percentage given in the table below (B)
Average weight Percentage deviation
A B
0.120g or less ± 10% (18 out of 20) ± 20% (2 out of 20)
More than 0.120g ± 7.5% (18 out of 20) ± 15%(2 out of 20)
.
• Method B
• The method B is for capsules containing liquid or base.
1. Weigh a capsule, open it without loss of shell material express as much of the contents is
possible.
2. Wash the shell with solvent ether, reject the washing.
3. Allow the shell to stand until all the odor of ether is no longer perceptible and weigh.
4. The difference between the whole weight and shell weight represents the weight of
contents.
5. Repeat the operation with further 9 capsules (total 10) and calculate the average weight
content of 10 capsules.
6. The weight of each capsule doesn’t differ from the average weight by more than 7.5%.
7. Except one capsule in which the weight of content may differ by not more than 15%.
8. Regardless of the weight of content of this type of capsules the percentage deviation
range should be between ±7.5 – ±15%.
Dissolution test
• The dissolution may be the rate limiting step in capsules absorption. Generally the
dissolution test of capsules is conducted in paddle or basket assembly. USP uses basket,
paddle, EP uses paddle, basket, and flow through cell apparatuses for solid dosage forms of
tablets and capsules.
• The dissolution test is carried out at 37oC ± 0.5oC. In general when basket apparatus is
used rotation speed is 100 rpm with 40 mesh screen of the basket. Other mesh sizes may
also be used if supported by necessary documentation. It is generally used for capsules and
floating type dosage forms or to those which tend to disintegrate slowly. For floating type of
dosage forms sinker may be used to prevent the floating of capsules.
• Samples are withdrawn according to specifications with tolerance of ± 5%. The test is
conducted on the equipment which was pre-calibrated with USP salicylic acid and
prednisone calibrator tablets (according to USP).
• The dissolution medium used should be deaerated and may be water, buffered aq.
Solution of pH 4 – 8 and dilute acid of 0.001N to 0.1N HCl. The test time is 30 – 60
minutes and with a single point specification or as specified in individual monographs.
.
• Procedure
1. Unless otherwise directed in the individual monograph, place 900ml fluid in the dissolution vessel.
2. Vessel should previously be immersed in water bath and allow dissolution temperature to come at 37oC ±
0.5oC.
3. Place one tablet or one capsule in the basket so that there is distance of 2.0 ± 0.2 cm between basket and
bottom of vessel.
4. Rotate the basket at a rate specified in the monograph.
5. Withdraw sample at the time indicated and analyze them by procedure described in the individual
monograph.
6. The dissolution testing is done in three stages of S1, S2, and S3.
7. In stage 1, 6 units are taken and the amount of drug from each unit should not be less than Q + 5% where Q
is the maximum amount of drug dissolved active ingredient specified in individual monograph.
8. Failure of first stage (if one or two tablets fail to comply) compensates to conductance of second stage S2
where additional 6 units are tested.
9. The avg. of 12 units in two stages should be equal to or greater than Q and no unit should be less than Q –
15%.
10. Failure of stage 2 leads to conductance of stage S3 where additional 12 units are tested and the avg. of total
units of three stages S1, S2 and S3 should be greater than or equal to Q and no two units should be less than
Q – 15% and none should be less than Q – 25%.
Note: Unless otherwise specified maintain the volume in vessel constant by adding a volume of
dissolution medium equivalent to that removed for sampling.

Stage Number tested Acceptance criteria

S1 6 Amount of drug released from each unit is not less
than Q + 5%.
S2 6 Avg. of S1+S2 (12 units) is equal to or greater than
Q and no unit is less than Q -15%.

S3 12 Avg. of S1+S2+S3 (24 units) is equal to or greater

than Q , not more than 2 units are less than Q – 15%
and no unit is less than Q - 25%.
.
• Dissolution testing of Soft gelatin capsules
• USP has recommended the use of apparatus 1 and 2, but since there had been
serious disadvantages related, attempts had been made in literature to develop new
methods for liquid filled soft gelatin capsules.
•

 Assay of API in capsules

1. Determine the amount of active ingredient by the method described in the assay.
2. Calculate the amount of API in the mixed contents of the capsules taken and
divide by the number of capsules taken.
3. The result should lie within the range specified in individual monograph.
• Sometime biological assay is described in the monograph e.g. drugs of natural
origin (vitamins, antibiotics, insulin etc.).
Quality control of powders
POWDER FLOW
• The widespread use of powder in the pharmaceutical industries has generalized a
variety of methods for characterizing powder flow.
• Several references appear in the pharmaceutical literature attempting to correlate
the various measures of powder flow to manufacturing properties. Powder
behavior is multifaceted and thus complicates the efforts to characterize the flow
properties of the pharmaceutical powders.
• In addition, no single or simple method can adequately characterize the flow
properties of pharmaceutical powders.
• Four common reported methods for testing powder flow rate are:
• - Angle of repose
• - Compressibility index or Hausner ratio
• - Flow rate through an orifice
• - Shear cell (Cylindrical, annular & plate)
.1. ANGLE OF REPOSE
• Angle of repose is a characteristic related to interparticulate
resistance or friction to movement between particles.
• Experimental difficulties arise as a result of segregation of material
and consolidation or aeration of the powder as the cone is formed.
• It is the constant three-dimensional angle (relative to horizontal base)
assumed by a cone like pile of material formed by any of several
different methods.
• Basic methods of angle of repose are as follows:
• - Static angle of repose
• - Drained angle of repose
• - Dynamic angle of repose
.• PROCEDURE FOR ANGLE OF REPOSE
• The base should be free from vibration. Vary the height of the funnel to
carefully build up a symmetrical cone of powder. Pour the powder sample
from the funnel to make a heap on paper.
• The funnel height should be maintained approximately 2 – 4 cm from the
top of powder pile as it is being formed in order to minimize the impact of
falling powder on the tip of the cone.
• If a symmetrical cone of powder cannot be successfully or reproducibly
prepared, this method is not appropriate. Determine the angle of repose
by measuring the height of the cone of powder and calculating the angle of
repose from the following equation:
tanθ = height/0.5 base
OR
θ = tan-1 h/R
.
• SPECIFICATIONS
• Although there is some variation in the qualitative description of
powder flow using the angle of repose, much of the pharmaceutical
literature appears to be consistent with the classification shown in
the table.
2. COMPRESSIBILITY INDEX & HAUSNER RATIO
.
• It is simple, fast and popular method of determining powder flow
characteristics.
• The compressibility index and the Hausner ratio are determined by
measuring both the bulk volume and the tapped volume of powder.
• The compressibility index and Hausner ratio are calculated using
measured values for bulk density and tapped density as fallows

Compressibility index = 100 × ( ρbulk − ρtap/ ρbulk )

Hausner ratio = ρtap/ ρbulk

For compressibility and Hausner ratio the generally accepted scale of flowability is
given in the table:
.
• 3. FLOW THROUGH AN ORIFICE (FLOWABILITY)
• The flow rate of a substance depends upon many factors some of which are
particle related and some related to the process.
• Monitoring the rate of flow of material through an orifice has been
proposed as a better measure of powder flowability.
• RECOMMENDED PROCEDURE FOR FLOW THROUGH AN ORIFICE
• Flow through an orifice is generally measured as the mass per time flowing
from any of a number of types of containers (cylinders, funnels, hoppers).
• It can be used only for that materials having some capacity to flow, it is not
useful for cohesive materials.
• - Use the cylinder as a container because the cylinder material should have
little effect on flow.
.
.