Manufacturing capsule shells

There are a number of companies manufacturing capsule shells for use in the pharmaceutical industry, and all produce capsules to standard sizes, which enables them to be filled on standard filling machines. There are eight sizes of capsules commercially available, listed in Table 11.19. The largest capsule size normally considered for oral administration is size 0, with the 00 and 000 capsules being difficult to swallow due to their size. 

Gelatin is produced by partial acid or partial alkaline hydrolysis of animal collagen. It has a wide variety of therapeutic and pharmaceutical uses. It is often used in the manufacture of hard and soft capsule shells, suppositories and tablets, and is sometimes used as a sponge during surgical procedures, as it can absorb many times its own weight of blood. 

Capsule shell sizes are generally standardized with Lnite volumes [12,13] available for dispensing the API or powder blend. The capsule size selection would depend on the dose and the bulk density of the NCE. Historically, if the doses were within a reasonable range, it was feasible to dispense API directly into the capsule body utilizing manual, semiautomatic, or automatic high-speed encapsulators available for manufacturing. 

Figures 23.3 through 23.5 illustrate the stepwise process low typically utilized in wet and dry granulation techniques for the manufacture of tablet dosage forms. For capsules, the process tends to be simpler with utilization of Lrst three steps from dry granulation followed by encapsulation in appropriate-size capsule shells. Depending on the batch size, a manual LHer (e.g., Bonapace), semiautomatic encapsulator (e.g., Capsugel Ultra 8), or automated encapsulator (Zanasi, Macofar, etc.) could be utilized for manufacturing.

Excipients that aid powder flow in tablet or capsule manufacture. Materials such as colloidal silica improve flow from hopper to die and aid packdown in the die or capsule shell. Accuracy and consistency of fill and associated dose is thereby improved. 

There are many advantages for choosing to develop and scale-up a capsule formulation over a tablet. As there is no need to form a compact that must withstand rigorous handling, development timelines can be reduced. Encapsulated products allow for easier blinding of clinical supplies and the ability to manufacture unique fills such as tablets in capsules, sustained release pellets, liquids, or semisolids. However, the costs of the capsule shells add an additional expense above the costs of tablet manufacture. 

Powders account for the majority of capsule fills and a number of quite disparate filling mechanisms have been developed unlike tabletting, where the principle of manufacture, compression between two punches in a die, is the same for all machines. The mechanisms can be divided into two broad groups, those that rely on the volume of the capsule shell to control the dose, known as capsule dependent, and those methods where the quantity of powder to be filled is measured away from the capsule, known as capsule independent. The dependent mechanisms require the capsule shell to be well filled to achieve weight uniformity and are less flexible than the independent methods. 

Unlike hard gelatin capsule shells which are manufactured empty and subsequently filled in a separate operation, soft gelatin capsules are manufactured and filled in one operation. This is a specialised process and tends to be performed by a limited number of companies. One consequence, therefore, of selecting a soft gelatin capsule formulation is that the product will probably be manufactured by a contract manufacturer. A desire to keep all manufacturing in-house is one of the reasons for companies considering the use of liquid-filled hard gelatin capsules as an alternative. 

Pullulan is used in coating for immediate release tablets and it is also used for preparation of capsule shells. An edible, mostly tasteless polymer, its chief commercial use is in the manufacture of edible films that are used in various breath freshener or oral hygiene products such as Listerine Cool Mint by Johnson Johnson (USA). 

An important class of materials that originates from the precursor core-shell particles is hollow capsules. Hollow capsules (or shells ) can be routinely produced upon removal of the core material using chemical and physical methods. Much of the research conducted in the production of uniform-size hollow capsules arises from their scientific and technological interest. Hollow capsules are widely utilized for the encapsulation and controlled release of various substances (e.g., drugs, cosmetics, dyes, and inks), in catalysis and acoustic insulation, in the development of piezoelectric transducers and low-dielectric-constant materials, and for the manufacture of advanced materials [14],... 

Hard shell capsules occupy a central role in drug product development and manufacture, ranking second behind compressed tablets in frequency of utilization in drug delivery. In product development, such capsules are often the first dosage form for any orally administered drug substance. Although the expectation may be that the final marketed form will be a compressed tablet, firms may consider using the capsule as the first marketed form to shorten the overall development cycle. 

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