18. What are the different ways of capsule sealing?

Industrial capsule-sealing machines are capable of producing 60,000 to 150,000 gelatin-banded,

heat-welded, or thermally coupled capsules per hour.
Gelatin-banded one manufacturer makes distinctive-looking capsules by sealing them with a
colored band of gelatin (Kapseals, Parke-Davis).
- if removed, the band cannot be restored without expert resealing with gelatin.
Heat-welded - a process that fuses the capsule cap to the body through the double wall
thickness at their juncture.
- it results in a distinctive ring around the capsule where heat welded.
Thermally coupled uses a liquid wetting agent (Lithium Carbonate) that lowers the melting
point in the contact areas of the capsules cap and body and then thermally bonds the two parts
using low temperatures (40C - 45C).
For extemporaneously prepared capsules, it may be sealed by lightly coating the inner surface
of the cap with a warm gelatin solution immediately prior to placement on the filled capsule
body.

19. What are the soft gelatin capsules?
Soft gelatin (also called softgel or soft elastic) capsules
- made of gelatin to which glycerin or polyhydric alcohol (e.g.
sorbitol) has been added.
- contain more moisture than hard capsules.
- may have a preservative, such as methyparaben and/or
propylparaben to retard microbial growth.
- comes in various shapes like oblong, oval, or round.
- may be single colored or two-toned and may be imprinted with
identifying markings.
- prepared with opaquants to reduce transparency and render characteristic features to the
capsule shell.
- used to encapsulate and hermetically seal liquids, suspensions, pasty materials, dry powders,
and even performed tablets.
- pharmaceutically elegant and easily swallowed.

20. Give the 2 methods of preparing soft gelatin capsules.
Plate process using a set of molds to form the capsules
1. A warm sheet of plain or colored gelatin is placed on the bottom plate of the mold and the
medication-containing liquid is evenly poured on it.
2. A second sheet of gelatin is carefully placed on top of the medication and the top plate of the
mold is put into place.
3. Pressure is then applied to the mold to form, fill, and seal the capsules simultaneously.
4. The capsules are removed and washed with a solvent harmless to the capsules.
Rotary or Reciprocating die process they are produced, filled and sealed in a continuous
operation.
- most soft gelatin capsules are prepared by the rotary die process, a method developed
in 1933 by Robert P. Scherer.
1. Liquid gelatin flowing from an overhead tank is formed into two continuous ribbons by the
rotary die machine and brought together between twin rotating dies.
2. At the same time, metered fill material is injected between the ribbons precisely at the
moment that the dies form pockets of the gelatin ribbons.
3. These pockets of fill-containing gelatin are sealed by pressure and heat and then severed
from the ribbon. (Use of ribbons of two different colors results in bicolored capsules)

















Schematic drawing of a rotary-die soft gelatin capsule filler (R.P. Scherer: Detroit, MI).
- the reciprocating die process is similar to the rotary process in that ribbons of gelatin
are formed and used to encapsulate the fill, but it differs in the actual encapsulating process.
1. The gelatin ribbons are fed between a set of vertical dies that continually open and close to
form rows of pockets in the gelatin riboons.
2. These pockets are filled with the medication and are sealed, shaped and cut out of the film as
they progress through the machinery.
3. As the capsules are cut from the ribbons, they fall into refrigerated tanks that prevent the
capsules from adhering to one another.

21. Enumerate the different liquids which can be encapsulated.
Water-immiscible volatile and non-volatile liquids vegetable and aromatic oils, aromatic and
aliphatic hydrocarbons, chlorinated hydrocarbons, ethers, esters, alcohols, and organic acids.
Water-miscible non-volatile liquids PEG, and non-ionic surface active agents (polysorbate 80).
Wter-miscible and relatively non-volatile compounds propylene glycol and isopropyl alcohol.
Depending on factors such as concentration used and packaging conditions.

- liquids that can easily migrate through the capsule shell are not suitable for softgel. (Water
above 5% and low-molecular-weight water-soluble and volatile organic compounds such as alcohols,
ketones, acids, amines and esters.

22. Give the criteria for materials which can be added to active ingredients.
1. Are harmless in the quantities used.
2. Do not exceed the minimum amounts required to provide their intended effect.
3. Do not impair the product bioavailability, therapeutic efficacy or safety.
4. Do not interfere with requisite compendial assays and tests.

23. What kinds of container should be used for dispensing capsules?
- the container may be required to be tight, well-closed, light resistant, and/or all of these.

24. Explain briefly the ff. tests for capsules:
a. Disintegration test follows the same procedure for uncoated tablets
capsules are placed in basket rack assembly, which is immersed 30 times per minute into a
thermostatically controlled fluid at 37C and observed over the time described in the individual
monograph.
b. Dissolution test follows the same dissolution medium for uncoated and plain-coated tablets
the contents of a specified number of capsules can be removed and the empty capsule shells
dissolved in the dissolution medium before proceeding with the sampling and chemical analysis.
c. Content uniformity amount of active ingredient is within the range of 85% - 115% of the
label claim for 9 of 10 dosage units assayed, with no unit outside the range of 70%-125% of the label
claim.
d. Weight variation for hard and soft capsules
HARD CAPSULES
- 10 capsules are individually weighed and their contents removed.
- the emptied shells are individually weighed and the net weight of the contents is calculated by
subtraction.
SOFT CAPSULES
- the gross weight of 10 intact capsules is determined individually.
- each capsule is cut open and the contents are removed by washing using a suitable solvent
(the solvent is allowed to evaporate at room temperature for 30 minutes)
- individual shells are weighed and the net contents calculated.
e. Moisture permeation test by packaging the dosage unit together with a color-revealing
desiccant pellet, exposing the package unit to relative-humidity over a specified time
- observing the desiccant pellet for color change and comparing the pretest and posttest weight
of the packaged unit.

25. What are the advantages of unit dose and strip packaging?
- provides sanitary handling of the medications
- ease of identification
- security in accountability for medications















Semi-automatic Strip Packaging Machine





Euclid Unit Dose Strip Packaging Machine

26. Name some of drug substances commercially prepared into soft gelatin capsules.
GENERIC NAME BRAND NAME
Acetazolamide Diamox Sequels
Amprenavir Agenerase Capsules
Cyclosporine Sandimmune
Cyclosporine Neoral
Digoxin Lanoxicaps
Ethosuximide Zarontin
Raniitidine HCl Zantac GELdose