Capsules PHARMACEUTICAL DOSAGE FORMS
〈1151〉 PHARMACEUTICAL DOSAGE FORMS This article is based on the requirement of the United State Pharmacopoeia. ( #usp , #pharmacopoeia , #MOA , #testprocedure , #qc , #qualitycontrol , #usp43 , #nf38 ) Capsules Capsules are solid dosage forms in which the drug substance and/or excipients are enclosed within a soluble container or shell or coated on the capsule shell. 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. This two-piece and one-piece capsule distinction, although imprecise, reflects differing levels of plasticizers in the two compositions and the fact that one-piece capsules typically are more pliable than two-piece capsules. The shells of capsules are usually made from gelatin. However, they may also be made from cellulose polymers or other suitable material. Most capsules are designed for oral administration. When no deliberate effort has been made to modify the drug substance release rate, capsules are referred to as immediate release. TWO-PIECE OR HARD-SHELL CAPSULES Two-piece capsules consist of two telescoping cap and body pieces in a range of standard sizes. ONE-PIECE OR SOFT-SHELL CAPSULES One-piece capsules typically are used to deliver a drug substance as a solution or suspension. Liquid formulations placed into one-piece capsules may offer advantages by comparison with dry-filled capsules and tablets in achieving content uniformity of potent drug substance(s) or acceptable dissolution of drug substance(s) with poor aqueous solubility. Because the contact between the shell wall and its liquid contents is more intimate than in dry-filled capsules, undesired interactions may be more likely to occur(including gelatin crosslinking and pellicle formation). MODIFIED-RELEASE CAPSULES The release of drug substance(s) from capsules can be modified in several ways. There are two categories of modified-release capsule formulations recognized by USP. Delayed-release capsules:
Capsules are sometimes formulated to include enteric-coated granules to protect acid-labile drug substances from the gastric environment or to prevent adverse events such as irritation. Enteric-coated multiparticulate capsule dosage forms may reduce variability in bioavailability associated with gastric emptying times for larger particles (i.e., tablets) and to minimize the likelihood of a therapeutic failure when coating defects occur during manufacturing. Alternatively, a coating may be applied to the capsule shell to achieve delayed release of the contents.
Extended-release capsules are formulated in such a manner as to make the contained drug substance available over an extended period of time following ingestion. Requirements for dissolution (see 〈711〉 ) are typically specified in the individual monograph. PREPARATION Two-piece capsules: Two-piece gelatin capsules are usually formed from blends of gelatins that have relatively high gel strength in order to optimize shell clarity and toughness or from hypromellose. They may also contain colorants such as Drug & Cosmetic (D&C) and Food, Drug, & Cosmetic (FD&C) dyes or various pigments, opaquing agents such as titanium dioxide, dispersing agents, plasticizers, and preservatives. Gelatin capsule shells normally contain between 12% and 16% water. The shells are manufactured in one set of operations and later filled in a separate manufacturing process. Two-piece shell capsules are made by a process that involves dipping shaped pins into gelatin or hypromellose solutions, followed by drying, cutting, and joining steps. Powder formulations for two-piece gelatin capsules generally consist of the drug substance and at least one excipient. Both the formulation and the method of filling can affect release of the drug substance. In the filling operation, the body and cap of the shell are separated before filling. Following the filling operation, the machinery rejoins the body and cap and ensures satisfactory closure of the capsule by exerting appropriate force on the two pieces. The joined capsules can be sealed after filling by a band at the joint of the body and cap or by a designed locking joint between the cap and body. In compounding prescription practice, two-piece capsules may be hand-filled. This permits the prescriber the choice of selecting either a single drug substance or a combination of drug substances at the exact dose level considered best for an individual patient. One-piece capsules: One-piece capsules are formed, filled, and sealed in a single process on the same machine and are available in a wide variety of sizes, shapes, and colors. The most common type of one-piece capsule is that produced by a rotary die process that results in a capsule with a seam. The soft gelatin shell is somewhat thicker than that of two-piece capsules and is plasticized by the addition of polyols such as glycerin, sorbitol, or other suitable materials. The ratio of the plasticizer to the gelatin can be varied to change the flexibility of the shell depending on the nature of the fill material, its intended usage, or environmental conditions. In most cases, one-piece capsules are filled with liquids. Typically, drug substances are dissolved or suspended in a liquid vehicle. Classically, an oleaginous vehicle such as a vegetable oil was used. However, nonaqueous, water-miscible liquid vehicles such as the lower molecular weight polyethylene glycols are now more common. The physicochemical properties of the vehicle can be chosen to ensure stability of the drug substance as well as to influence the release prole from the capsule shell. Note: The detailed information regarding individual Official Dosage Forms in subsequent articles, Visit our website https://www.pharmaceuticalguideline.com/ regularly.