FOR PHARMACY STUDENTS

1. By
V. Manoj Kumar
3rd
year
Pharm. D

2. CAPSULES
●
Capsules are solid dosage forms in which the drug formulation in a
powder, solution or suspension, a combination of miscible liquid, or a
simple liquid formulation is enclosed in a shell. Depending on the
composition of the gelatin shell, the capsules can be hard or soft gelatin
capsules. Hard gelatin capsules are typically used for powder or solid
fills, whereas soft gelatin capsules are used for semisolid or liquid fills.
Lately, hard capsules have also been used for liquid or semisolid fills.
In capsule formulation development and during filling of capsules, a
number of quality control tests are performed to ensure that capsules
produced meet the requirements as specified in official compendium and
conventional requirements established by the industries over the years.
These tests will be discussed in three stages: in-process testing,
finished product testing and shelf-life testing.

3. ADVANTAGES
●
Capsules mask the taste and odour of unpleasant drugs and can
Capsules mask the taste and odour of unpleasant drugs and can
be easily
be easily
●
They are slippery when moist and hence easy to swallow with a
They are slippery when moist and hence easy to swallow with a
draught of water
draught of water
●
As compared to tablets, less adjuncts are required.
As compared to tablets, less adjuncts are required.
●
The shells are physiologically inert and easily and quickly
The shells are physiologically inert and easily and quickly
digested in the gastrointestinal tract.
digested in the gastrointestinal tract.
●
They are economical.
They are economical.
●
They are easy to handle and carry.
They are easy to handle and carry.
●
The shells can be opacified (with titanium dioxide) or coloured, to
The shells can be opacified (with titanium dioxide) or coloured, to
give protection from light.
give protection from light.

4. DISADVANTAGES
DISADVANTAGES
●
The drugs which are hygroscopic absorb water from the capsule
The drugs which are hygroscopic absorb water from the capsule
shell, making it brittle and hence are not suitable for filling into
shell, making it brittle and hence are not suitable for filling into
capsules.
capsules.
●
The concentrated solutions which require previous dilution are
The concentrated solutions which require previous dilution are
unsuitable for capsules because if administered as such lead to
unsuitable for capsules because if administered as such lead to
irritation of stomach.
irritation of stomach.

5. ●
It is the department in the Pharmaceutical
company where the quantity analyst attempts
to determine the concentration of a specific
substance
QUANTITY CONTROL OF
CAPSULES

6. Quality control tests are divided
into
PHYSICAL TESTS
●
Disintegration test
●
Weight variation
CHEMICAL TESTS
●
Dissolution test
●
Assay
●
Content uniformity
●
Stability testing
●
Moisture permeation
test

7. .
PHYSICAL TESTS OF CAPSULES
.

8. Finally physical control procession and packing may be
accomplished by the following in the line continuous
operations
●
The capsules diameter sorter allows to pass to the next unit
of any capsules within + or – 0.020 inches of theoretical
diameter.
●
Capsules colour
The capsules are fed to it automatic from the diameter
sorter by a pneumatic conveyer. In this unit, any capsule
whose colour does not conform to the reference colour
standard for that particular product is discarded, others will
passes the test.

9. IN-PROCESS QUALITY CONTROL TESTS FOR CAPSULES
DRUG PRODUCTS
In-process quality control tests for capsule drug products are carried out at
In-process quality control tests for capsule drug products are carried out at
predefined intervals during the product manufacturing, by the manufacturing
predefined intervals during the product manufacturing, by the manufacturing
personnel, and their results recorded on the batch record. Adverse findings in
personnel, and their results recorded on the batch record. Adverse findings in
these tests can be used as a guide to altering the manufacturing-process
these tests can be used as a guide to altering the manufacturing-process
parameters.
parameters.
During the encapsulation of soft gelatin capsules, the following parameters are
During the encapsulation of soft gelatin capsules, the following parameters are
usually closely monitored and controlled:
usually closely monitored and controlled:
●
Gel ribbon thickness and uniformity across the ribbon
Gel ribbon thickness and uniformity across the ribbon
●
Soft gels seal thickness at the time of encapsulation
Soft gels seal thickness at the time of encapsulation
●
Weight of the capsule fill and its variation from capsule-to-capsule.
Weight of the capsule fill and its variation from capsule-to-capsule.
●
Weight of the capsule shell and its variation from capsule-to-capsule.
Weight of the capsule shell and its variation from capsule-to-capsule.
●
Moisture level of the capsule shell before and after drying
Moisture level of the capsule shell before and after drying
●
Visual inspection, fill weight, and fill weight uniformity are the key in-
Visual inspection, fill weight, and fill weight uniformity are the key in-
process tests used for hard gelatin capsules
process tests used for hard gelatin capsules

10. DISINTEGRATION TEST
DISINTEGRATION TEST
●
The disintegration test determines whether capsules disintegrated
with a prescribed time when placed in a liquid medium under the
prescribed integral conditions.
METHOD
According to B.P. and which applies to both hard and soft
capsules
●
Introduces one capsule in each tube and suspend the apparatus
in a beaker containing 60ml water at 37 C,
if hard capsules float on surface of water, the disc may be added
●
Operate the apparatus for 30 min, remove the assembly from the
liquid.

11. POTENCY AND IMPURITY CONTENT
POTENCY AND IMPURITY CONTENT
Soft gelatin capsules are tested for drug content (potency, as a percent of
Soft gelatin capsules are tested for drug content (potency, as a percent of
label claim). In addition, most drug products are tested for related
label claim). In addition, most drug products are tested for related
substances are impurities. These must meet predefined specifications for
substances are impurities. These must meet predefined specifications for
batch to be acceptable
batch to be acceptable
PERMEABILITY AND SEALING
PERMEABILITY AND SEALING
Soft gelatin capsules are tested for physical integrity (absence of
Soft gelatin capsules are tested for physical integrity (absence of
leakage) by visual inspection. Similarity, hard gelatin capsules are
leakage) by visual inspection. Similarity, hard gelatin capsules are
tested for any breach of physical integrity (breakage or opened cap
tested for any breach of physical integrity (breakage or opened cap
and body)
and body)

13. WEIGHT VARIATION TEST
WEIGHT VARIATION TEST
The uniformity of dosage units may be demonstrated by determining
The uniformity of dosage units may be demonstrated by determining
weight variation or content uniformity. The weight variation method
weight variation or content uniformity. The weight variation method
is as follows.
is as follows.
WEIGHT VARIATION TEST FOR SOFT GELATIN CAPSULES
WEIGHT VARIATION TEST FOR SOFT GELATIN CAPSULES
For soft gelatin capsules, the gross weight of 10 gelatin capsules is
For soft gelatin capsules, the gross weight of 10 gelatin capsules is
determined individually. Then each capsule is cut open with a suitable
determined individually. Then each capsule is cut open with a suitable
clean, dry cutting instrument (e.g., scissors or a sharp open blade), and
clean, dry cutting instrument (e.g., scissors or a sharp open blade), and
the contents are removed by washing with a suitable solvent (that
the contents are removed by washing with a suitable solvent (that
dissolves the fill but not the shell). The solvent is allowed to evaporate at
dissolves the fill but not the shell). The solvent is allowed to evaporate at
room temperature over a period of about 30 minutes, followed by
room temperature over a period of about 30 minutes, followed by
weighing of the individual washed shells. The net contents are calculated
weighing of the individual washed shells. The net contents are calculated
by subtraction and the content of active ingredient in each capsules can
by subtraction and the content of active ingredient in each capsules can
be determined by calculation based on the percent drug content in the
be determined by calculation based on the percent drug content in the
formulation.
formulation.
Fill-weight variation of the capsules is often a function of the equipment
Fill-weight variation of the capsules is often a function of the equipment
setup and filling operation. An automated capsule sizing machine and /or
setup and filling operation. An automated capsule sizing machine and /or
weight checker is frequently used to discard over-or under filled capsules.
weight checker is frequently used to discard over-or under filled capsules.

14. UNIFORMITY OF CONTENT
UNIFORMITY OF CONTENT
This test is performed only when the content is specified in the
This test is performed only when the content is specified in the
individual monographs and when capsules fail weight variation
individual monographs and when capsules fail weight variation
test. If the weight of capsules is completely filled no need of this
test. If the weight of capsules is completely filled no need of this
test.
test.
Unless otherwise stated in the monograph for an individual
Unless otherwise stated in the monograph for an individual
capsule, the amount of drug substance, determined by assay, is
capsule, the amount of drug substance, determined by assay, is
within the range of 85.0% to 115.0%of the label claim for nine(9) of
within the range of 85.0% to 115.0%of the label claim for nine(9) of
the ten(10) dosage units assayed, with no unit outside the range of
the ten(10) dosage units assayed, with no unit outside the range of
75.0% to 125.0% of the labelled drug content. Additional tests are
75.0% to 125.0% of the labelled drug content. Additional tests are
prescribed when two or three dosage units are outside of the
prescribed when two or three dosage units are outside of the
desired range but within the stated extremes.
desired range but within the stated extremes.

15. D
DISSOLUTION TESTS FOR CAPSULES
ISSOLUTION TESTS FOR CAPSULES
Drug adsorption and physiological availability depend on the drug
Drug adsorption and physiological availability depend on the drug
substance being in the dissolved state at the site of drug adsorption. The
substance being in the dissolved state at the site of drug adsorption. The
rate and extent of dissolution of the drug from the capsule dosage form is
rate and extent of dissolution of the drug from the capsule dosage form is
tested by a dissolution test. This test provides means of quality control in
tested by a dissolution test. This test provides means of quality control in
ensuring that, different batches of the drug product have similar drug
ensuring that, different batches of the drug product have similar drug
release characteristics and also, a batch has similar dissolution as the
release characteristics and also, a batch has similar dissolution as the
batch of capsules that was shown initially to be clinically effective.
batch of capsules that was shown initially to be clinically effective.
MOISTURE CONTENT
MOISTURE CONTENT
Water content of the entire capsule or the capsule contents are
Water content of the entire capsule or the capsule contents are
determined by Karl Fisher titrimetry to enable the correlation of water
determined by Karl Fisher titrimetry to enable the correlation of water
content with the degradation profile or drug-release characteristics of the
content with the degradation profile or drug-release characteristics of the
capsules.
capsules.

16. MICROBIAL CONTENT
MICROBIAL CONTENT
The capsules are tested to ensure lack of growth of the bacteria and the
The capsules are tested to ensure lack of growth of the bacteria and the
mould by microbiological tests. These tests are usually carried out by
mould by microbiological tests. These tests are usually carried out by
Incubation of the capsule contents in the growth medium and counting
Incubation of the capsule contents in the growth medium and counting
the colonies formed after a predefined period of time. Selection of the
the colonies formed after a predefined period of time. Selection of the
growth medium and duration of the test, as well as maintaince of
growth medium and duration of the test, as well as maintaince of
aseptic conditions during the testing, are critical to successful
aseptic conditions during the testing, are critical to successful
assessment
assessment
of microbial contamination by this method.
of microbial contamination by this method.

17. THANK YOU
THANK YOU