A Review of the Problem, Test Methods, and Solutions

www.pharmtech.com anufacturers of pharmaceutical products have the responsibility — not only from marketing and ethical standpoints but also from a legal (regulatory) perspective — to ensure that their products meet dissolution specifications during storage conditions described on the label. This is necessary because dissolution per se is rate determining in terms of the absorption and bioavailability of a drug. Unfortunately, a few dosage forms exist in which eventual change in the dissolution characteristics is a common problem. Formulations containing gelatin in the outer layer (i.e., hard and soft gelatin capsules) as well as sugar-coated tablets are typical examples. The problem has been ascribed to cross-linking of gelatin, which occurs with time. Because of this tendency, the very use of gelatin in pharmaceutical formulations has been put to question. Nevertheless, the material is used widely despite efforts to replace it with other substances. This article reviews the literature describing the widespread problem of a drop in dissolution rates of gelatin-containing products and critical observations concerning their in vitro and in vivo behavior. The discussion includes a brief introduction to gelatin, some reported instances of altered dissolution profiles, the chemistry of change, responsible factors, suggested test methods, and reported solutions to the problem.