REGULATING DRUG-RELEASE VIA NONUNIFORM DISTRIBUTION OF COATING COMPOSITION IN MULTILAYER DRUG COATED GRANULES

Multilayer drug-coated granules with a non-uniform distribution of the coating composition specifically the drug loading and the polymer vis cosity, across the thickness of the film matrix were prepared by the f luidized bed coating process. The rate and duration of diphenhydramine hydrochloride release from the coated granules can be modified throug h control of the gradient change in the coating composition across the thickness of the methylcellulose (MC) film matrix. A steeper gradient change across the film matrix resulted in a slower overall release ra te. Formulations with gradient drug loading distribution exhibited an extended release time that can be twice as long as that for the contro l formulation. Gradient layered matrices obtained by sequentially depo siting different viscosity grades of MC produced release profiles that differed from film matrices prepared using MC blends.