Powder-filled hard-shell capsules often have been assumed to have better bioavailability than tablets. Most likely, this assumption is derived from the fact that the shell rapidly dissolves and ruptures, which affords at least the potential for rapid release of the drug, together with the lack of use of a compaction process comparable to tablet compression in filling the capsules. However, capsules can be just as easily malformulated as tablets. There have been number of reports of bioavailability problems with capsules (10-13).
Powder-filled hard-shell capsules allow for a degree of flexibility of formulation not obtainable with tablets: Often they are easier to formulate because there is no requirement that the powders be formed into a coherent compact that must stand up to handling like tablets. However, it must be recognized that the problems of powder blending and homogeneity, powder fluidity, and lubrication in hard-capsule filling are similar to those encountered in tablet manufacture. The ability of such dry solids to be uniformly filled into a dosing-disc cavity or dosing tube is the determining factor in weight variation and, to a degree, content uniformity.
Modern capsule-filling technology makes possible the filling of various combinations of diverse systems, for example, beads/granules, tablets, liquid/semisolids, small soft-gelatin capsules, or even smaller hard-shell capsules into hard-shell capsules. Such multicomponent capsules offer many possibilities in dosage form design (14).
Incompatibilities can be overcome by separating problem ingredients within the same capsule; for example, one component could be filled as a coated pellet. Various modified or controlled drug delivery systems can be created by incorporating modified-release beads or granules. Immediate-release and sustained-release formulations of a drug can be included in the same capsule. In another possible configuration, two different drugs whose pharmacokinetic properties require different modified-release profiles can be filled into the same capsule as different species of beads. Indeed, capsules are ideally suited to the dispensing of granular or bead-type modified-release products since they may be filled without a compression process that could rupture the particles or otherwise compromise the integrity of any controlled-release coatings.
Traditionally the province of soft-shell capsules, the filling of liquids into hard-shell capsules, made feasible through improvements in encapsulation and sealing technology, has become a topic of substantial interest today. As will be discussed later, the liquid filling of capsules of either type offers numerous advantages, such as the ability to manage low melting point drugs, enhance the content uniformity of low-dose drugs, and enhance the bioavailability of poorly soluble, hydrophobic drugs.
Hard-shell capsules also may be used to advantage as unit-dose containers for delivering dry powder drugs by inhalation (15,16). Micronized drug with carrier powder is released for inhalation in dry powder inhaler (DPI) devices that either cut or puncture the shell walls (17). Such systems are used to deliver asthma and allergy drugs like sodium cromolyn, and may prove advantageous for delivering large, labile, biological molecules that are difficult to deliver by other means.
Hard-shell capsules are widely used in preliminary drug studies. Phase I development studies are often carried out with hard-shell capsule formulations because of their relative ease of formulation and manufacture, even though the final formulation often may be intended to be a compressed tablet. For conventional filling machines, fillers and other excipients are often needed, especially when doses are small in relation to capsule shell volumes. In a recent development, Capsugel has introduced a new filling machine, the Xelodose® microdosing system for the precise direct filling of doses as low as 100 mcg without the need for excipients (18). This development provides very broad flexibility for dispensing different doses for phase I clinical studies while minimizing the potential for interactions with excipients.
Hard-shell capsules also are uniquely suitable for blinded clinical tests. Bioequivalence studies of tablet formulations may be conveniently "blinded" by inserting tablets into opaque capsules, often along with an inert filler powder. Even capsule products may be disguised by inserting them into larger capsules.
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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.