Phar Dose Report

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 g elatin. 

capsule cap to the body through the double double wall Heat-welded - a process that fuses the capsule thickness at their juncture. - it results in a distinctive ring around the capsule where heat welded.

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Thermally coupled – uses a liquid wetting agent (Lithium Carbonate) that lowers the melting point in the con tact areas of the capsule’s cap and body and then thermally bonds the two parts

using low temperatures (40⁰C - 45⁰C). 

For extemporaneously extemporaneously prepared capsules, it may be sealed by lightly coat ing 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 me thyparaben 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 o f 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 mo ld 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 pre pared 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 t he 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 c olors 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 t hat 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 t he 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 e ncapsulated. 

Water-immiscible volatile and non-volatile liquids – vegetable and aromatic oils, aromatic and aliphatic hydrocarbons, chlorinated hydrocarbons, ethers, esters, alcohols, and organic acids.

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Water-miscible non-volatile liquids – PEG, and non-ionic surface active agents (polysorbate 80).

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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 co mpendial 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 c apsules:

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 37⁰C 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 we ight 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