Cellulose Matrices for Zero-Order Release of Soluble Drugs

Abstract

Release of two very soluble beta adrenergic blockers namely: metoprolol tartrate and alprenolol HCl from cellulose matrices containing hydroxypropylcellulose (HPC) or sodium carboxymethylcellulose (Na CMC) or methylcellulose (MC), or MC + Na CMC or HPC + Na CMC in different ratios was studied in distilled water using USP dissolution apparatus 2. Increase in the ratio of total polymer to drug has decreased the release rate in a nonlinear manner. When only one polymer (HPC or Na CMC) was used, the release profiles were of first-order or sigmoidal in nature respectively. MC matrices disintegrated in < 1 h. By mixing the drug with an optimum amount of the nonionic (HPC or MC) and anionic (Na CMC) polymers, zero-order release profiles with excellent reproducibility were obtained. Rate of erosion of the matrix was 2.5 times higher when drug, Na CMC and HPC were present compared to the matrix containing only drug and HPC. This indicates that the diffusional pathlength for the drug increases with time when HPC alone was present and the former might be constant when an optimum percent of nonionic (HPC or MC) and anionic (Na CMC) polymers were present in the matrix.