Gelatin shell

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],... 

Soft gelatin capsules are not an inexpensive dosage form, particularly when compared to direct compression tablets [3]. There is a more intimate contact between the shell and its liquid contents than exists with dry-filled hard gelatin capsules, which increases the possibility of interactions. For instance, chloral hydrate formulated with an oily vehicle exerts a proteolytic effect on the gelatin shell however, the effect is greatly reduced when the oily vehicle is replaced with polyethylene glycol [3]. 

Reported in vitro dissolution failures due to cross-linking of gelatin shells that did not result in bioinequivalence [42,45] serve as another set of examples, although based on a different mechanism, that suggests that significant in vitro differences do not necessarily translate to in vivo differences. 

As mentioned, hydrolysis is the other important mechanism by which some lipids (glycerides and phosphoglycerides) degrade and can lead to a reduction in pH due to liberation of free fatty acids this was discussed in Chapter 10 (Part I Parenteral Application). This phenomenon is less important for oral formulations when compared to parenteral products, since the former generally have low amounts of water in the formulation. Hydrolysis could occur on storage if water is absorbed from or through the gelatin shell. 

Lalla J. K. and S. U. Bhat. 1995. Protracted disintegration of hematinic capsules in soft gelatin shells. Part 1. Gelatin-mineral interactionindian Drugs, 32 320-327. 

Colorants can be divided into water-soluble dyes and water-insoluble pigments. Some of the insoluble colors or pigments can also provide opacity to tablet coatings or gelatin shells, which can promote stability of light-sensitive active materials. Pigments such as the iron oxides, titanium dioxide, and some of the aluminum lakes are especially useful for this purpose. 

The filling material must be compatible with the gelatin shell and, therefore, deliquescent or hygroscopic materials cannot be used. Conversely, due the moisture content in the capsule shells, they cannot be used for moisture-sensitive drugs. All ingredients need to be free of even trace amounts of formaldehyde to minimize cross-linking of gelatin. 

Capsules Small-dose bulk powder enclosed in gelatin shell, active ingredient plus diluent Internal... 

This section will discuss the formulation principles of Softgels, including gelatin shell and fill formulations. 

The wet gel mass is manufactured by mixing together and melting, under vacuum, the gelatin shell ingredients (gelatin, plasticizer, water, colorants and sometimes opacifiers, flavors, and preservatives). At the encapsulation machine (Fig. 5), molten gel mass flows through heated transfer tubes and is cast onto... 

Fig. 11 The behavior of dissolution of gelatin shell with time at different temperatures. Key O, initial , sample stored for 6 mo at 25° C , sample stored for 6 mo at 40°C and , sample stored for 6 weeks at 60°C. (From Ref p. 1498. Reprinted by courtesy of the authors and The Pharmaceutical Society of Japan.)...

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