Pharmaceutical Capsules: Dosage Forms

• Capsules are solid dosage forms with medicinal agents and/or inert substances enclosed in a gelatin shell.
• Gelatin shells can be hard or soft.
• Capsules are shaped like a cylinder with hemispherical ends, also known as a sphero-cylinder.

Advantages of Capsules

• Elegant and conveniently carried.
• Easily identified.
• Easily swallowed without needing spoons or measuring devices.
• Tasteless and odorless when swallowed, masking the taste/odor of medicinal agents.
• Available in various strengths, providing flexibility and accurate dosing.
• Packaged and shipped at lower cost and with less breakage than liquid dosage forms.
• More stable and have a longer shelf life than liquid counterparts.

Hard Gelatin Capsules

• Used in most commercial medicated capsules.
• Commonly used in clinical drug trials.
• Used by pharmacists in extemporaneous compounding.
• Made of gelatin, sugar, and water.
• Can be clear, colorless, and tasteless.
• Can be colored with FD&C and D&C dyes.
• Can be made opaque by adding titanium dioxide.
• Most commercial capsules contain colorants and opaquants for distinctive looks.

Gelatin

• Obtained by partial hydrolysis of collagen from animal skin, connective tissue, and bones.
• Available as a fine powder, coarse powder, shreds, flakes, or sheets.
• Stable in dry air but subject to microbial decomposition when moist.
• Hard gelatin capsules contain 13% to 16% moisture.
• High humidity can distort capsules, while extreme dryness can make them brittle.
• Should be stored in an environment free from excessive humidity or dryness.

Moisture Effects and Gelatin Administration

• Moisture absorption can affect hygroscopic agents within capsules so desiccants are often included.
• Desiccants used are dried silica gel, clay, and activated charcoal.
• Prolonged exposure to high humidity can affect in vitro capsule dissolution.
• Gelatin softens in cold water, absorbing up to 10 times its weight in water.
• Gelatin is soluble in hot water and warm gastric fluid, rapidly dissolving to expose contents.
• Gelatin, a protein, is digested by proteolytic enzymes and absorbed.

Manufacture of Hard Gelatin Capsule Shells

• Made in two sections: the capsule body and a shorter cap.
• The two parts overlap when joined.
• Shells are industrially produced by mechanically dipping pegs into a temperature-controlled melted gelatin mixture.
• Pegs are made of manganese bronze and affixed to plates.
• Plates are lowered to the gelatin bath to achieve the proper length and thickness of coating.
• Gelatin is dried by temperature- and humidity-controlled air.
• Dried capsule parts are trimmed and removed from pegs, then bodies and caps are joined.
• The thickness of gelatin walls must be strictly controlled for a snug fit.
• Cap-forming pegs are slightly larger than body-forming pegs.
• Capsule shell production involves continuous dipping, drying, removing, and joining.

Capsule Shapes and Designs

• Conventional hard gelatin capsules are cylindrical with hemispherical ends.
• Manufacturers can create distinctive-looking capsules by altering the shape of capsule-making pegs.
• Tapered ends on the body-producing peg create differentiated capsules.
• Capsules with locking grooves (or indentations) have been prepared such as snap fit and coni snap fit capsules to ensure reliable closing

Snap-fit Capsules

• Feature concentric locking rings on the body and cap to prevent reopening after filling.
• Grooves fit into each other to ensure reliable closing.

Coni-Snap Capsules

• Improved form of Snap-Fit with a slightly tapered capsule body rim.
• Have a rounded hemispherical end that is stronger and more resistant to deformation.

Coni-Snap Supro Capsules

• The upper capsule part extends far over the lower part, concealing most of it.
• Designed to be smaller and more secure, with difficult separation of the two parts.
• Offer less gripping surface, increasing security and integrity.

Capsule Sizes

• Empty gelatin capsules are manufactured in various lengths, diameters, and capacities.
• Size is determined by the amount of fill material.
• Density and compressibility of the fill determine how much can be packed.
• Comparison with known powders can help estimate needed capsule size.
• Final determination may require trial and error.
• For human use, sizes range from 000 (largest) to 5 (smallest).
• Larger capsules are available for veterinary use.
• Permit a wide number of options for the physician/pharmacist.
• 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

• Divided into developing the formulation and selecting the capsule size, filling the capsule shells, sealing and polishing.
• Capsule fill weight = tapped density of formulation X capsule volume

Developing the Capsule Formulation

• Goal is accurate dosage, good bioavailability, ease of filling, stability, and elegance.
• Active and inactive components must be blended thoroughly.
• Blending is especially important for low-dose drugs.
• Preformulation studies determine if bulk powders can be blended effectively or require particle size reduction/processing.
• Similar density and particle size of drug/nondrug components are advantageous.
• Powder mix/granules must be free-flowing.

Excipients

• Diluents/Fillers: Provide bulk and cohesion (e.g., lactose, microcrystalline cellulose, starch).
• Disintegrants: Assist in breakup and distribution of contents (e.g., pregelatinized starch, croscarmellose).
• Lubricants/Glidants: Enhance flow properties (e.g., fumed silicon dioxide, magnesium stearate, talc).
• Wetting Agents: Improve dissolution (e.g., sodium lauryl sulphate).
• Magnesium stearate can retard penetration by gastrointestinal fluids and delay drug dissolution so a wetting agent may be added.

Encapsulation of Different Ingredients

• Tablets or small capsules can be inserted into capsules to separate incompatible agents or add premeasured drug amounts.
• Coated pellets designed for modified-release drug delivery are commonly placed in capsule shells.
• Gelatin capsules are unsuitable for aqueous liquids. However, some liquids, such as fixed or volatile oils, that do not interfere with the stability of the gelatin shells may be placed in locking gelatin capsules (or the capsules may be sealed with a solution of gelatin thinly coating the interface of the cap and body) to ensure retention of the liquid.
• Liquids can be mixed with an inert powder to make a wet mass/paste.
• Eutectic mixtures can be mixed with a diluent or absorbent to separate interacting agents and absorb liquefied material.

Extemporaneous Compounding of Prescriptions

• Calculate for one or two more capsules than required to compensate for powder loss.
• If the dose of the drug is inadequate to fill the volume of the capsule body, a diluent is added.

Filling Hard Capsule Shells

• When filling a small number of capsules in the pharmacy, the pharmacist may use the punch method.
• Count the capsules to be filled from the stock container
• It means that by counting the capsules as the initial step rather than taking a capsule from stock as each one is filled, the pharmacist guards against filling the wrong number of capsules and avoids contaminating the stock container with drug powder.
• The powder is formed on a clean paper/plate into a cake.
• The empty capsule body is punched vertically into the powder cake repeatedly until filled.
• The pharmacist should punch each capsule in the same manner and weigh after capping.
• The First filled capsule should be weighed and all later capsules should be equal in weight.
• Weigh each capsule when using potent drugs to ensure accuracy.
• Granular material that does not lend itself to the punch method of filling capsules may be poured into each capsule from the powder paper on which it is weighed.

Capsule Sealing

• Some manufacturers make tamper-evident capsules by sealing the joint between the two capsule parts.
• Some capsules are sealed with a colored band of gelatin
• Industrial capsule sealing machines can produce 60,000 to 150,000 sealed capsules per hour.

Capsule Identification

• Capsules and tablets are imprinted with names/monograms of the manufacturer and the assigned national drug code number.

Cleaning and Polishing Capsules

• Small amounts of powder may adhere to the outside of capsules.
• Capsules may be cleaned individually with a clean gauze or cloth.

Soft Gelatin Capsules

• Made of gelatin with glycerin or a polyhydric alcohol (e.g., sorbitol).
• Contain more moisture than hard capsules.
• May contain a preservative to retard microbial growth (e.g., methylparaben, propylparaben).
• May be oblong, oval, or round.
• May be single colored or two-toned and may be imprinted with identifying markings.
• Used to encapsulate and hermetically seal liquids, suspensions, pasty materials, dry powders, and even preformed tablets.

Uses of Soft Gelatin Capsules

• Can contain a variety of liquid, paste, and dry fills.
• Liquids include water-immiscible volatile/nonvolatile liquids, water-miscible nonvolatile liquids, and water-miscible relatively nonvolatile compounds.
• Solids may be encapsulated as solutions in suitable liquid solvent, suspensions, dry powders, granules, pellets, or small tablets.
• Liquids that can easily migrate through the capsule shell are not suitable.
• These materials include water above 5% and low-molecular-weight water-soluble and volatile organic compounds such as alcohols, ketones, acids, amines, and esters.

Compendial Requirements for Capsules: Added Substances

• Substances added to official preparations/capsules must be harmless, used in minimum amounts, not impair bioavailability, therapeutic efficacy, or safety, and not interfere with assays/tests.

Enteric Coated Capsules

• Coated to resist dissolution in gastric fluids but release contents in the intestine.
• Useful for maintaining stability of medications unstable in acidic conditions, minimizing side effects, delayed action, and facilitating colonic drug delivery.
• Typical materials used for enteric coating are shellac, cellulose acetate phthalate, and fatty waxy materials, poly vinyl acetate phthalate, hydroxy propyl methyl cellulose phthalate etc.

Counting Capsules

• Capsules may be counted manually or by automated equipment.
• Specially designed trays are used for counting small numbers of solid dosage units.

Examples of Capsules

• Amoxicillin: Hard gelatin cap, 250/500mg, antibiotic.
• Erythromycin Estolate: Enteric coated hard gelatin capsule, 250mg, antibiotic.
• Fluoxetine HCl: Tapered capsule body hard gelatin capsule, 10/20/40mg, antidepressant.
• Indomethacin: Enteric coated hard gelatin capsule, 25/50mg, anti-inflammatory/analgesic.
• Pancreatin: Enteric coated micropellets capsules, 150/300mg, digestive enzymes.
• Omeprazole: Enteric coated hard capsule, 20/40mg, proton pump inhibitor.
• Omega 3: Soft gelatin capsule, 1000mg, nutrient.
• Vitamin D3: Soft gelatin capsule, 1000/2000/5000/10000 IU, nutrient.