Drug release from a multiparticulate pellet system.

Abstract

Multiparticulate pellet systems are used as both immediate and modified release dosage forms. Previous work has classified uncoated pellet systems prepared from microcrystalline cellulose as an inert matrix. The Higuchi square root of time equation, derived to describe drug release from a single planar system, is the accepted method to evaluate drug release from both planar and spherical heterogeneous inert granular matrices. A second equation of interest, the Higuchi cubic equation, was derived to describe drug release from a spherical pellet. Both equations predict a linear relationship between drug release and the square root of time or time. The purpose of the present study was to evaluate drug release from a multiparticulate pellet system using both equations and to study any differences when both equations are used to describe the same drug release data. By evaluating dissolution data from various pellet mesh cuts representing different bead radii and surface areas, changes in the slopes of both plots would be expected. Pellets were manufactured using extrusion/spheronization technology and consisted of 90% microcrystalline cellulose and 10% acetaminophen. Statistical comparison indicates that the Higuchi cubic equation seems to be more sensitive to changes in pellet size. While the square root of time equation describes the drug release data from granular, inert, spherical pellets, it may be better to utilize the Higuchi cubic equation because it is more sensitive to changes in particle size.