Floating granules of ranitidine hydrochloride-gelucire 43/01: formulation optimization using factorial design.

The purpose of this research was to develop and optimize a controlled-release multiunit floating system of a highly water soluble drug, ranitidine HCl, using Compritol, Gelucire 50/13, and Gelucire 43/01 as lipid carriers. Ranitidine HCl-lipid granules were prepared by the melt granulation technique and evaluated for in vitro floating and drug release. Ethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose were evaluated as release rate modifiers. A 3(2) full factorial design was used for optimization by taking the amounts of Gelucire 43/01 (X (1)) and ethyl cellulose (X (2)) as independent variables, and the percentage drug released in 1(Q(1)), 5(Q(5)), and 10 (Q(10)) hours as dependent variables. The results revealed that the moderate amount of Gelucire 43/01 and ethyl cellulose provides desired release of ranitidine hydrochloride from a floating system. Batch F4 was considered optimum since it contained less Gelucire and was more similar to the theoretically predicted dissolution profile (f(2) = 62.43). The temperature sensitivity studies for the prepared formulations at 40 degrees C/75% relative humidity for 3 months showed no significant change in in vitro drug release pattern. These studies indicate that the hydrophobic lipid Gelucire 43/01 can be considered an effective carrier for design of a multiunit floating drug delivery system for highly water soluble drugs such as ranitidine HCl.