8/26/2021

Mr. A.V. SURENDRA

M.Pharm, (PhD)
Assistant Professor
K L College of Pharmacy
K L University

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Close length test

Length of capsule is measured by vernier caliper
capable of measuring upto 0.02 mm.

Finishing / sorting out:

Capsules should be subjected to evaluation of

appearance & tested as per compendia requirements.
Capsules are allowed to pass through capsule colour
sorter which is discarding capsules whose colour does
not confirm to reference colour standard.

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diameter test
Capsule diameter sorter allows to pass to next unit any
capsule within ±0.020 inch-of theoretic diameter of
particular capsule being tested.

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PaCkaging & labeling:

Type of primary & secondary packaging materials &
labeling particulars should be checked & cross
contamination should be avoided at this stage.

Packed & labeled capsules should be collected at

regular time intervals of same shift & checked for
packaging integrity & label content.

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ph
pH between 2.5 & 7.5, since preparations that are more
acidic can cause hydrolysis & leakage of gelatin shell
& preparations that are more alkaline can tan gelatin &
affect solubility of shell.

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raw materials For outer shell & Filling

material:
Raw materials like gelatin, plasticizers used for
capsule shell production should be tested for their
compliance with pre determined specifications like
bloom strength, viscosity, impurity profile, microbial
load, moisture content etc.

Components of filling material should be tested

according to compendia specifications.

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Filling oF CaPsules:
Filling capacity of hard gelatin capsules should be
determined as it can be filled with a range of material,
granules , pellets, tablets, semi solid materials, pastes.
Fill weight is influenced by the nature of the
formulation & tapped density of formulation.
drying:
Temperature & humidity in drying areas should be
monitored.
Moisture level & capsule strength after drying should
be determined.
Bloated capsules &capsules with soft spot should be
removed at this stage.
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miCrobiologiCal testing
Total bacterial count does not exceed 500 C.F.U per
gram with E. coli & S.alm.

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solubility tests

Solubility limits for empty capsules as follows:

(a) Water resistance fails to dissolve in water at 20 to
30°C in 15 min;

(b) Acid solubility-dissolves in less than 5 min in

0.5% aqueous HCl (w/w) at 36 to 38°C.

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Formaldehyde test
Formalin treatment has been employed to modify
solubility of gelatin capsules.

 Exposure to formalin vapors or treatment with aque

ous formalin results in an unpredictable decrease in
solubility of gelatin film, owing to cross-linkage of
gelatin molecule initiated by aldehyde.

This result may also be noted if product being filled

contains aldehydic materials, or if aldehyde flavorants
are added.

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bloom or gel strength

It is measure of cohesive strength of cross-linking that
occurs b/w gelatin molecules.
Bloom α M.W. of gelatin.
determination
Measuring weight in grams required to move
plastic plunger that is 0.5 ’’ in diameter 4 mm into a 6
2/3 % gelatin gel that has been held at l0°C for 17 h
limit: 150 to 250 g.
Higher Bloom strength  more physically stable is
capsule shell.
Cost of gelatin α Bloom
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VisCosity oF gelatin
Viscosity of 6 2/3 % gelatin in water solution at
600C is measure of molecular chain length &
determines manufacturing characteristics of gelatin
film.

General range of viscosity 25 to 45 millipoise, it may

be within narrow range 38  2 millipoise.

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iron Content
Iron is always present in new gelatin & its
concentration usually depends on iron content of large
quantities of water used in its manufacture.

limit: Gelatin used for soft gelatin capsules should not

contain more than 15 ppm of iron.
disadVantages:
(i) react with certified dyes.
(ii) with organic compounds to produce color (e.g. with
phenolic compounds).

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base adsorPtion test

Number of grams of liquid base required to produce a
capsulatable mixture when mixed with 1 gram of
solid(s).
FaCtors
Solid's particle size & shape,
Physical state (fibrous, amorphous, or crystalline),
Density
Moisture content
Oleophilic or hydrophilic nature.
In determination of base adsorption, solid(s) must be
completely wetted by liquid base.
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Weigh 40 g of solid into a 150-ml tared beaker.

In a separate 150-ml tared beaker, place about 100 g
of liquid base.
 Add small increments of base to solid & using
spatula, stir base into solid after each addition until
solid is thoroughly wetted & uniformly coated with
base.
 This should produce mixture that has soft oint
ment-like consistency.
 Continue to add liquid and stir until mixture flows
steadily from spatula blade when held at a 45-
degree angle above mixture.

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base adsorption= Weight of Base/ Weight of Solid.

Base adsorption is used to determine
"minim per gram" factor (M/g) of solid(s).
minim Per gram FaCtor
volume in minims that is occupied by 1 gram (S) of
solid plus weight of liquid base (BA) required to make
capsulatable mixture.
M/g = (BA+S/W) ХV
Weight of base = BA
Gram of solid = S
Weight of mixture (W)
CC= 16.23 minims (V).
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Lower base adsorption of solid(s) & higher density

of mixture, smaller capsule will be.

seal thiCkness
Seals are measured under microscope & changes in
ribbon thickness, heat, or die pressure are made if
necessary.

Acceptable seal thickness is 1 half to 2 thirds of ribbon

thickness.

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Fill weight CheCks

Weighing whole fresh capsule, slitting it open &
expressing contents.

Shell is then washed in suitable solvent (petroleum

ether) & empty shell is reweighed.

If necessary, adjustments in pump stroke can

be made to obtain proper fill weight.

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moisture Content
Moisture content of shell is determined by toluene
distillation method.

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Wcapsule – Wemptied shell = Wcontent

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Content uniFormity
30 Capsules are selected, 10 of which are assayed by
specified procedure.

Requirements are met if 9 of 10 are within

specified potency range of 85 to 115%, & tenth is
not outside 75 to 125%.
If > 1, but < 3, of first 10 capsules fall outside 85 to
115% limits, remaining 20 are assayed.

Requirements are met if all 30 capsules are within

75 to 125% of specified potency range, & not < 27 of
30 are within 85 to 115% range. 101

101

disintegration test For CaPsules:

Place 1 capsule in each of 6 tubes of basket &
suspend assembly in water maintained at 37+/-2c.
 Do not use disc for hard capsules except when hard
capsule float on top of water, disc may be added.
 When testing soft capsules disc may be used.
Operate apparatus for 30min  soft capsule & 60
min  hard capsules.
Capsule passes test if no residue is left on screen of
apparatus or if residue in form of fragments of shell.
If 1 or 2 capsules fails to disintegrate, repeat test on
12 additional capsules so as not < 16 of total number of
18 capsules tested get disintegrated.
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CaPsule disintegration tester

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dissolution test For CaPsules:

Place 1000 ml of water free from dissolved air having
a temperature of 36.5-37.5 C in to vessel.
 Place specified no of capsules in dry basket.
Assemble apparatus.
Start motor & adjust its speed to 100 rpm or such
other speed given in monograph.

With that of required volume of solution from vessel

after 5 min or after period specified in monograph.

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Filter & determine amount of active ingredient

present by method given by monograph repeat
complete operation for 3 times.

Sample passes test if amount of active ingredients in

solution is not < 75% of stated amount given in
monograph.

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dissolution test aPParatus

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STAGE TABLETS LIMITS

Stage -1 6 not < Q +5%. Accept
(S1)
Stage -2 6+6 Avg 12 >= Q Accept
(S2) no single unit <
Q-15%.
Stage -3 12+12 Avg 24 > = Q. Accept
(S3) not > 2 < Q-
15%. no unit is <
Q - 25%.
• Q  monograph tolerance limit.
• Dissolution tolerance in USP/NF is not < 75%
dissolved in 45 min.
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aCCelerated PhysiCal stability tests

Effect of capsule content on gelatin shell.
Tests are strictly relevant to integrity of gelatin shell
& should not be construed as stability tests for active
ingredients in capsule content.
Test conditions are
(1) 80% RH at room temperature in an open container;
(2) 40°C in an open container;
(3) 40°C in a closed container (glass bottle with tight
screw-cap).

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Capsules at these stations are observed periodically for

2 weeks.
Both 'gross & subtle effects of storage conditions on
capsule shell are noted & recorded.

Control capsule should not be affected except at 80%

RH station, where capsule shell, since as moisture is
absorbed, capsules become softer, tackier, & bloated.

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