Hard shell capsules

The experiments above are rather easy to carry out and should always be part of a preformulation program, since hygroscopicity can be so important that it will dictate whether or not a particular salt should be used. Dalmane, for instance, is a monosulfate and is used as such since the disulfate, desirable in many other respects, is so hygroscopic that it will remove water from a hard-shell capsule and make it exceedingly brittle. 

Although capsules made from gelatin predominate, recent years have seen an increased interest in and availability of nongelatin capsules. Such alternative shell compositions may satisfy religious, cultural, or vegetarian needs to avoid animal sources. Hard shell capsules made from starch were developed by... 

Hard shell capsules have often been assumed to have better bioavailability than tablets. Most likely this assumption derives from the fact the gelatin shell rapidly dissolves and ruptures, which affords at least the potential for rapid release of the drug, together with the lack of utilization of a compaction process comparable to tablet compression in filling the capsules. However, capsules can be just as easily malformulated as tablets. A number of cases of bioavailability problems with capsules have been reported [5-8],... 

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 will stand up to handling. However, the problems... 

The dose of the drug and its solubility are important considerations in the design of the formulation. The amount and type of active ingredient influences capsule size and the nature and amount of excipients to be used in the formulation. Larger-dose drugs that must be granulated to produce tablets may be more easily direct-filled into hard shell capsules with proper choice of excipients. 

KS Murthy, RG Reisch, Jr., MB Fawzi. Dissolution stability of hard-shell capsule products. Part II the effect of dissolution test conditions on in vitro drug release. Pharm Technol 13(6) 53-58, 1989. 

Practical Considerations in the Scale-Up of Powder-Filled Hard Shell Capsule Formulations... 

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. 

In a survey of industry practices, Heda (12) found that, as a matter of policy, 46% of the firms sampled favor direct filling of powders as a first choice over granulation prior to filling capsules. Thirty-six percent of firms allow formu-lators to make that decision at their own discretion, whereas 18% of firms favor granulation of all formulations prior to encapsulation. Yet, for half of the firms responding, only 0 10% of their hard shell capsule products are direct-fill powder formulations, and only 27% of firms reported that more than 50% of their capsules were developed as direct-fill formulations. Although some of these non-direct-fill formulations may be controlled release formulations, e.g., barrier-coated bead products, difficult powder formulation problems may, at least in part, account for this observation. 

Small LE, Augsburger LL. Aspects of the lubrication requirements for an automatic capsule-filling machine. Drug Devel Ind Pharm 1978 4 345. Tattawasart A, Armstrong NA. The formation of lactose plugs for hard shell capsules. Pharm Devel Tech 1993 2 335-343. 

Murthy, K. S., Reisch, R. G., and Fawzi, M. B. (1989), Dissolution stabihty of hard-shell capsule products Part I The effects of exaggerated storage conditions, Pharm. Technol., 13(3), 72-86. 

Podczeck, F. Jones, B.E. The in vitro dissolution of theophylline from different hard shell capsules. Drug Dev. Ind. Pharm. 2002, 28, 1163-1169. 

Hard-shell capsule (phase I clinical trials) followed by prototype tablet dosage form... 

Chopra R, Podczeck F, Newton JM, et al. The influence of pellet shape and film coating on the filling of pellets into hard shell capsules. Eur J Pharm Biopharm 2002 53 327-33. 

Murthy KS, Enders NA, Fawzi MB. Dis.solulion Stability of Hard-shell Capsule Products, Part I The Effect of Exaggerated Storage Conditions. Pharm Tech 1989 Mar 72-86. 

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