Capsules: Solid Dosage Form

• Capsules are a solid dosage form with medicinal agents and/or inert substances enclosed in a small shell of gelatin
• Gelatin capsule shells can be hard or soft, depending on their composition

Advantages of Capsules

• Elegant and conveniently carried, readily identified, and easily taken
• Easily swallowed, so there is no need for spoons or other measuring devices
• Tasteless and odorless when swallowed
• Packaged and shipped by manufacturers at lower cost and with less breakage
• Available for many medications in a variety of dosage strengths, providing flexibility to the prescriber and accurate individualized dosage for the patient
• Stable and have a longer shelf life than their liquid counterparts

Hard Gelatin Capsules

• Used in most commercial medicated capsules
• Employed in clinical drug trials to compare the effects of an investigational drug with those of another drug product or placebo
• Community pharmacists use hard gelatin capsules in the extemporaneous compounding of prescriptions

Hard Gelatin

• The empty capsule shells are made of gelatin, sugar, and water
• They can be clear, colorless, and essentially tasteless
• May be colored with various dyes and made opaque by adding agents such as titanium dioxide (opaquant)
• Most commercially available medicated capsules contain combinations of colorants and opaquants to make them distinctive, many with caps and bodies of different colors

Effect of Moisture on Gelatin

• Moisture may be absorbed by gelatin capsules and affect hygroscopic agents within
• Many capsules are packaged with a small packet of a desiccant material to protect against the absorption of atmospheric moisture
• Desiccant materials most often used are dried silica gel, clay, and activated charcoal
• Prolonged exposure to high humidity can affect in-vitro capsule dissolution
• Changes have been observed in capsules containing tetracycline, chloramphenicol, and nitrofurantoin
• Capsules subjected to such stress conditions must be evaluated case by case

Gelatin Administration

• Gelatin softens in cold water through the absorption of water up to 10 times its weight, even though it is insoluble
• Some patients prefer a capsule wetted with water or saliva because a wetted capsule slides down the throat more readily than a dry capsule
• Gelatin is soluble in hot water and in warm gastric fluid; a gelatin capsule rapidly dissolves and exposes its contents
• Gelatin, being a protein, is digested by proteolytic enzymes and absorbed

The Manufacture of Hard Gelatin Capsule Shells

• Hard gelatin capsule shells are manufactured in two sections, the capsule body and shorter cap
• The two parts overlap when joined, with the cap fitting snugly over the open end of the capsule body
• Shells are produced industrially by the mechanical dipping of pins or pegs of the desired shape and diameter into a temperature-controlled reservoir of melted gelatin mixture
• When dried, each capsule part is trimmed mechanically to the proper length and removed from the pegs, and the capsule bodies and caps are joined together

Capsule Shapes

• A manufacturer may prepare distinctive-looking capsules by altering the usual rounded shape of the capsule-making pegs
• By tapering the end of the body-producing peg while leaving the cap-making peg rounded, one manufacturer prepares capsules differentiated from those of other manufacturers
• Another manufacturer uses capsules with the ends of both the bodies and caps highly tapered

Capsule Sizes

• For human use, empty capsules ranging in size from 000 (the largest) to 5 (the smallest) are commercially available
• Larger capsules are available for veterinary use
• For prescriptions requiring extemporaneous compounding, hard gelatin capsules permit a wide number of options for the physician
• The pharmacist may compound capsules of a single medicinal agent or combination of agents at the precise dosage prescribed for the individual patient

Preparation of Filled Hard Gelatin Capsules

• Preparation of filled hard gelatin capsules is divided into the following general steps:
• Developing and preparing the formulation and selecting the capsule size
• Filling the capsule shells
• Capsule sealing (optional)
• Cleaning and polishing the filled capsules

Developing the Capsule Formulation

• Goal is to prepare a capsule with:
• Accurate dosage
• Good bioavailability
• Ease of filling and production
• Stability
• Elegance

Encapsulation of Different Ingredients

• Inserting tablets or small capsules into capsules is sometimes useful in the commercial production of capsules and in a pharmacist's extemporaneous preparation of capsules
• May be done to separate chemically incompatible agents or to add premeasured amounts of potent drug substances
• Rather than weighing a potent drug, a pharmacist may choose to insert a prefabricated tablet of the desired strength in each capsule
• On an industrial scale, coated pellets designed for modified-release drug delivery are also commonly placed in capsule shells
• Examples of fill in hard gelatin capsules:
• Powder or granulate
• Pellet mixture
• Paste
• Capsule
• Tablet