Chapter 7: Capsules

- When medications are to be administered orally to adults, capsules and tablets usually are preferred because they are conveniently carried, readily identified, and easily taken.

- Most capsules and tablets are tasteless when swallowed, which is not the case with oral liquid medication.

• Capsules

  • are solid dosage forms in which medicinal agents and/or inert substances are enclosed in a small shell of gelatin.

  • Gelatin capsules may be hard or soft, depending on their composition.

  • The shells may be composed of two pieces, a body and a cap, or they may be composed of a single piece.

  • Two-piece capsules are commonly referred to as hard-shell capsules, and one-piece capsules are often referred to as soft-shell capsules.

  • When no deliberate effort has been made to modify the API release rate, they are referred to as immediate release.

• Hard Gelatin Capsules

  • used in most commercial medicated capsules.

  • They are also commonly employed in clinical drug trials to compare the effects of an investigational drug with those of another drug product or placebo.

  • The empty capsule shells are made of gelatin, sugar, and water. As such they can be clear, colorless, and essentially tasteless.

    • They maybe colored with various FD&C AND D&C dyes and made opaque by adding agents such as titanium oxide.

  • There are also vegetarian capsules which are cellulose-based and not made from animal by-products for vegetarian and vegan consumers.

  • Vegetarian capsules have no known potential health risks and generally consist of hydroxypropyl methylcellulose (HPMC) and purified water.

  • They are fast dissolving and easily digestible as well as Kosher and Halal certified, GMO free, gluten free, and contain no preservatives.

  • Gelatin is obtained by the partial hydrolysis of collagen obtained from the skin, white connective tissue, and bones of animals. In commerce, it is available in the form of a fine powder, a coarse powder, shreds, flakes, or sheets.

    • Is stable in air when dry but is subject to microbial decomposition when it becomes moist. Normally, hard gelatin capsules contain 13% to 16% moisture.

    • If stored in an environment of high humidity, additional moisture is absorbed by the capsules, and they may become distorted and lose their rigid shape.

    • In an environment of extreme dryness, some of the moisture normally present in the gelatin capsules is lost, and the capsules may become brittle and crumble when handled.

  • Prolonged exposure to high humidity can affect in vitro capsule dissolution. Such changes have been observed in capsules containing tetracycline, chloramphenicol, and nitrofurantoin.

  • Although gelatin is insoluble, it does soften in cold water through the absorption of water up to 10 times its weight of water.

  • Number of methods developed to track the passage of capsules and tablets through the gastrointestinal tract.

    • Gamma Scintigraphy - a noninvasive procedure that entails the use of a gamma ray-emitting radiotracer incorporated into the formulation with a gamma camera coupled to a data recording system.

    • Pharmacoscintigraphic - evaluation provides information about the transit and drug-release patterns of the dosage forms as well as the rate of drug absorption from the various regions of the gastrointestinal tract.

      • useful in a. determining whether a correlation exists between in vitro and in vivo bioavailability for immediate release products.

      • b. assessing the integrity and transit time of enteric-coated tablets through the stomach en route to the intestines.

      • c. drug and dosage form evaluation in new product development.

    • Heidelberg capsule

      • uses a pH-sensitive nondigestible radiotelemetric device.

      • No. 0 gelatin capsule. It has been used as a nonradioactive means to measure gastric pH, gastric residence time, and gastric emptying time of solid dosage forms in fasting and nonfasting human subjects.

• The manufacture of Hard Gelatin Capsule Shells

  • Hard gelatin capsule shells are manufactured in two sections, the capsule body and a shorter cap. The two parts overlap when joined, with the cap fitting snugly over the open end of the capsule body. Some capsule shells are designed to lock in place when closed.

  • The pegs, made of manganese bronze, are affixed to plates, each capable of holding up to about 500 pegs.

  • Pulvules, Eli Lilly - By tapering the end of the body-producing peg while leaving the cap-making peg rounded.

  • Spansule, Capsules, SmithKline Beecham - uses capsules with the ends of both the bodies and caps highly tapered.

  • Original Snap-Fit - enables the two halves of the capsule shells to be positively joined through locking grooves in the shell walls.

  • Coni-Snap Capsule - in which the rim of the capsule body is not straight but tapered slightly. This reduces the risk of the capsule rims touching on joining and essentially eliminates the problem of splitting during large-scale filling operations.

  • Coni-Snap Supro capsules - the upper capsule part extends so far over the lower part that only the rounded edge of the latter is visible.

• 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.

• Preparation of Filled Hard Gelatin Capsules

  1. Developing and preparing the formulation and selecting the capsule size.

  2. Filling the capsule shells.

  3. Capsule sealing (optional)

  4. Cleaning and polishing the filled capsules.

• Developing the Formulation and Selecting the Capsule Size

  • Care in blending is especially important for low-dose drugs, because lack of homogeneity in blending may result in significant therapeutic consequences.

  • A diluent or filler may be added to the formulation to produce the proper capsule fill volume. Lactose, microcrystalline cellulose, and starch are commonly used for this purpose.

  • Disintegrants are frequently included in a capsule formulation to assist the breakup and distribution of the capsule’s contents in the stomach. Among the disintegrants used are pregelatinized starch, croscarmellose, and sodium starch glycolate.

  • Milling

    • r