1.

CONTENTS
2. • INTRODUCTION • ADVANTAGES • DISADVANTAGES • QUALITY
CONTROL OF CAPSULES Physical tests Chemical tests •
PACKAGING OF CAPSULES • PHARMACEUTICAL ASPECTS 3
3. 4. 4 DEFINITION •
Capsule is the most versatile of all dosage forms
4. . Capsules are solid dosage forms in which one or more medicinal and
inert ingrédients are enclosed in a Small Shell or container usually
made of gelatin. 4
5. 5. 5 ADVANTAGES OF CAPSULES •
6. Capsules mask the taste and odour of unpleasant drugs and can be
easily administered. •
7. They are slippery when moist and hence easy to swallow with a
draught of water. • As compared to tablets less adjuncts are required. •
The shells are physiologically inert and easily and quickly digested in
the gastrointestinal tract. • They are economical . • They are easy to
handle and carry. • The shells can be opacified (with titanium dioxide)
or coloured, to give protection from light. 5
8. 6. 6 DISADVANTAGES OF CAPSULES
9. The drugs which are hygroscopic absorb water from the capsule shell
making it brittle and hence are not suitable for filling into capsules. The
concentrated solutions which require previous dilution are unsuitable
for capsules because if administered as such lead to irritation of
stomach. 6
10. 7. 7 OFFICAL CAPSULE COMERCIAL AVAILABILITY
STRENGTHS CATEGORY
11. Amoxicillin Wymox 250-500 mg Antibacterial
12. Ampicilin Omnipen 250-500 mg Antibacterial Aspirin 300 mg
Analgesic
13. Cephalexin Keflex 250-500 mg Analgesic Cloxacillin sodium
Tegopen 250-500 mg Antibacterial Dipenhydramine HCL Benadryl
HCL 25-50 mg Antihistamine 7 SOME EXAMPLES OF OFFICAL
CAPSULES
14. 8. 8 QUALITY CONTROL OF CAPSULES
15. 9. 9 QUALITY CONTROL OF CAPSULES Whether capsules are
produced on a small scale or large scale all of them are required to
 pass through certain tests i.e., quality control tests to test the quality of
the finished product. 9
16. 10. 10 Quality control tests are divided into PHYSICAL TEST •
Disintegration test • Weight variation CHEMICAL TEST • Dissolution
test • Assay • Content uniformity • Stability testing • Moisture
permeation test 10
17. 11. 11 PHYSICAL TESTS OF CAPSULES 11
18. 12. 12 Finally physical control processing and packing may be
accomplished by the following in line continuous operations 1.A
capsule diameter sorter allows to pass to the next unit of any capsule
with in + or _ 0.020 inch of theoretical diameter .
19. 2.A capsule 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 passes the test. 12
20. 13. 1313 DISINTERATION TEST-
21. • The disintegration test determines the whether capsules
disintegrated with a prescribed time when placed in a liquid medium
under the prescribed integral conditions .
22. METHOD- • According to B.P and which applies to both hard and
soft capsules
23. 1.introduce one capsule in each tube and suspend the apparatus
in a beaker containing 60ml water at 370 C, – if hard capsules float on
surface of water, the disc may be added.
24. 2.Operate the apparatus for 30 min, remove the assembly from
the liquid.
25. 3.the capsule pass the test if • No residue remains on the screen
of the apparatus or, • If the residue remains, it consists of fragments
shells , • If a soft mass with no palpable core , • If the disc is used any
residue is remaining on its lower surface should only consists of
fragments of shells. 14

26. 16. 16 WEIGHT VARIATION FOR HARD CAPSULES

27. weigh 20 capsules individually and determine the avg weight The
individual wts should be with in limit of 90-110% of avg wt If not all of
capsules fall with in the limits,
28. Weigh 20 capsules individually Remove the net content of each
capsule with the aid of a small brush Weigh the empty shells
individually NET WT OF CONTENTS INDIVIDUALLY = THE WT OF
SHELL-GROSS WT 16
29. 17. 17 Determine the avg net content from the sum of individual
net wt Then determine the difference b/w each individual net content
and avg net content
30. LIMITS- • Not more then 2 of the differences are greater then
10% of the avg net content • No case is the difference greater then
25% wt range 17
31. 18 If more then 2 ,but not more then 6 capsules deviate from the
avg b/w 10-25% Determine the net contents of an additional 40
capsules Determine the avg content of entire 60 capsules Determine
the 60 deviations from the new avg LIMITS- • NMT 6 of 60 capsules
does the difference exceed 10% of the avg net content • No case does
the difference exceed 25% 18
32. . 19 FOR SOFT CAPSULES
33. proceed as directed under hard capsules, but determine the net
wt of the contents of individual capsules as follows: weigh the capsules
individually then cut and open the capsules remove the contents by
washing with the suitable solvent allow the solvents to evaporate from
the shells at room temp weigh the individual shells Calculate the net
contents 19
34. 20. 20 CHEMICAL TESTS OF CAPSULES 20
35. 21. 21 DISSOLUTION TEST- •
36. The dissolution test is carried out using the dissolution apparatus
official in both the U.S.P and I.P . • The capsule is placed in a basket ,
and the basket is immersed in the dissolution medium and caused to
rotate at a specified speed . • The dissolution medium is held in a
covered 1000ml glass vessel and maintained at 370 c +-0.5 0c by
means of a constant temperature suitable water bath . • The stirrer
speed and type of dissolution medium are specified in the individual
monograph . 21
37. 22. 22 RESULT –
38. • Six capsules are tested and are accepted if each of them is not
less than monograph specified i.e., p +5% • If it fails then additional six
capsules are tested the result is accepted if the avg. of 12 capsules is
 greater than or equal to p and none of them is less than p-15%. • If the
capsule still fails the test the additional 12 capsules are tested and are
accepted if the avg. of 24 is greater than to p, if not more than two less
than p-15% and none of them is less than p- 25% 22

39. 26. 26 FACTORS AFFECTING DRUG DISSOLUTION FROM

HARD GELATIN CAPSULES Overall Dissolution Rate is a Function of:
• Dissolution Rate of the Shell • Rate of Penetration of Dissolution
Medium • Rate of Deaggregationof Powder Mass • Nature of Primary
Drug Particles
40. 27. 27 • Normally, shell ruptures and dissolves within about 4
minutes. • Rupture occurs first at the shoulders where shell wall is
thinnest. • Ends fall away and as liquid penetrates and deaggregation
occurs, formulation tend to spill out of the two ends.
41. 28. 28 CONTENT UNIFORMITY 10 capsules are taken and
subjected to assay 9 of 10 capsules should be in the range of +_ 15%
(85-115%) And 10th capsule are beyond +_ 15% range then 20
capsules are assayed All capsules with in range of +_25% (75-125%)
28
42. 29. 29 MOISTURE PERMEATION TEST The degree and rate of
moisture penetration is determined by packaging the dosage unit
together with a colour revealing desiccant pellet Expose the packed
unit to known relative humidity over a specified time Observe the
desiccant pellet for colour change Any change in colour indicates
absorption of moisture By measuring pre test weight and protest
weight of pellet, amount can be calculated. 29
43. 30. 30 BLOOM STRENGHT OF GELATIN RAW MATERIALS-
The gelatin of the capsule shells should be assayed for varies physical
properties like bloom strength ,viscosity etc.. PROCEDURE- gelatin is
weighed into water to typically create a 6.67% soln in standard bloom
bottles The mix is then stirred and keep it for 3 hours at room temp
Bottles are placed in a 650 c bath for 20 minutes 30
44. 31. 3131 Allow the bloom jars to cool for 15 min at room temp
They are then conditioned for 16 hrs in 100 c water bath
45. 32. 32 when conducting gelatin bloom test, the bloom jar is
centred with the probe just above the sample surface The probe
penetrates the gelatin to a target depth of 4mm at a speed of 0.5mm/s
 , and then retracts The peak force is the gel strength in grams bloom
32
46. 33. 33 CAPSULES PHYSICAL STABILITY • Unprotected soft
gelatin capsules rapidly reach equilibrium with the atmospheric
conditions under which they are stored. • This inherent characteristic
warrants a brief discussion of the effects of temp and humidity on the
products. • General statements relative to the effects of temp and
humidity on soft gelatin capsules must be confined to a control capsule
that contains mineral oil with a gelatin shell having a dry glycerin to dry
gelatin ratio of 0.5-1 and water to dry gelatin ratio of 1-1 and that is
dried to equilibrium with 20-30% RH and 21-24o c. 33
47. 34. 34 • The physical stability of soft gelatin capsules is
associated primarily with the pick up or loss of water by the capsule
shell . • If these are prevented by proper packaging ,the above
controlled capsule should have satisfactory physical stability at S temp
ranging from just above freezing to as high as 600 c. • As the humidity
increases the moisture content pickup of capsules increases . ex- at
30%RH at room temp shows that gelatin retain about12%(48 mg) of
water and glycerin 7%(14 mg)of water. at 60%RH the moisture content
should be 17.4%. • High humidity (>60%RH at 21-240 c )produce more
lasting effects on the capsule shell. 34
48. 35. 35 Since as moisture is absorbed ,the capsules become softer
,tackier , and bloated. • The capsule manufacturer routinely conducts
accelerated stability tests on new product as an integral part of the
production development program. • The successful results are
obtained by conducing at test conditions like 1.80%RH at room temp in
an open container 2.400 c in open container 3. 400 c in closed
container (glass bottle with tight screw cap) 35
49. 36. 36 chemists conducting the physical stability test in their own
lab should keep two important points in mind 1.prior to testing ,the
capsule should be equilibrated to known atm conditions, preferably 20-
30%RH at 21-240 c. 2.evaluation of the results of the previously
described heat test should be made only after the capsules have
returned to equilibrium to room temp 36
50. 37. 3737
51. 38. 38 PACKAGING OF CAPSULES 38
52. 39. 39 PACKAGING AND STORAGE OF CAPSULES Capsules
should be packed in a well-closed glass or plastic containers and
stored in a cool place. • These type of containers have advantage over
cardboard boxes that they are more convenient to handle and
transport and protect the capsules from moisture and dust. • To
prevent the capsules from rattling a tuft of cotton is placed over and
under the capsules in the vials. • In vials containing very hygroscopic
capsules a packet-containing desiccant like silica gel or anhydrous
calcium chloride 39
53. 40. 40 may be placed to prevent the absorption of excessive
moisture by the capsules. • Now a days capsules are strip packaged
which provide sanitary handling of medicines, ease in counting and
identification . 40
54. 41. 4141 • Plastic bottle with screw cap (most popular package in
USA) • Clam shell blister (one piece plastic that folds over and locks
itself; no heating required)
55. 42. 42 • Blister pack (heat sealed blister on a cardboard) • Plastic
pail/bucket( economical bulk package) • Plastic pouch zip locked (for
sale via retail stores or route trucks must be packed in outer case for
shipping ) 42
56. 43. 4343
57. 44. 44 PHARMACEUTICAL ASPECTS 44
58. 45. 45 PHARMACEUTICAL ASPECTS – Essentially capsules are
solid dosage form containing liquid medication and therefore offer
certain advantages 1.They permit liquid medications to become easily
portable. 2.These capsules easily pass the appropriate compendial
tests and surpass other solid dosage form ,because liquid formulations
can be more accurately and precisely compounded, blended,
homogenized and measured or dispensed then can dry solid
formulations 45
59. 46. 46 3.Dissolution and disintegration- The majority of drugs
were more rapidly and completely available for dissolution from the soft
gelatin capsule then from the commercial tablets and capsules in
accordance to dissolution and disintegration time. the dissolution on
capsules of chloramphenicol, using the modified USP apparatus
(rotating bottle method), showed that 46 •soft gelatin capsules brand to
 releases •Hard shell capsule brands B2 and D releases 22.3 to 24.8%
in 30 min 100.7% and 87.2%
60. 47. 47 4. The physiologic availability of drugs is often improved by
liquid drug substance i.e., it contains the drug in liquid form or in
suspension. Nelson ,in his review, points out that the availability of a
drug for absorption of solid dosage forms decreases as below:
SOLUTION>SUSPENSION>POWDER FILLED
CAPSULE>COMPRESSED TABLET >COATED TABLET absorption
profile Ex-1.bioavailability study of digoxin soft gelatin capsules and
tablets were reported by Astorri, and that in heart patients using
digoxin ,absorption of digoxin from

48. 48 the capsulated solution was 36% higher than the tablet, while in healthy
volunteers it was 20% higher then tablets. Ex-2. The bioavailability of theophylline
from soft gelatin capsule in comparison to a commercially available liquid
aminophylline preparation and to a non-alcoholic Aminophylline were studied and
found that two dosage forms were bioequivalent as measured by the area under the
plasma level time curves. This shows that capsule providing a convenient portable
dosage form for a liquid medication.
61. 49. 49 • 5.The pharmaceutical chemist should certainly consider
the bioavailability potential of soft gelatin formulations. The
biopharmaceutical characteristics of such formulations can be altered
easily than solid dosage forms . Through the selection and use of
liquids and combinations of liquids that range from water immiscible
through emulsifiable to completely water miscible and by altering the
type and quantity of thickening or suspending agents . • 6.Orally
administered drugs, particularly if used chronically ,can be irritating to
the stomach .The dosage form of such drugs can affect gastric
tolerance.
62. 50. 50 When compared the ulcerogenic potential of soft gelatin
capsule of dexamethasone with tablet the capsule had reduced
ulcerogenic potential.