Pilocarpine release from hydroxypropyl-cellulose-polyvinylpyrrolidone matrices

Abstract

Characteristics of pilocarpine release from cast plasticized hydroxypropylcellulose (HPC) and HPC-polyvinylpyrrolidone (PVP) matrices were studied using tritiated pilocarpine. Increased concentration of PVP and decreased molecular weight of HPC accelerated release of pilocarpine from the matrices. The aqueous solution penetrated rapidly into the matrices, which swelled rapidly to their equilibrium volumes. With increased molecular weight and concentration of HPC in the matrices, the rate of solvent penetration decreased and swollen volume of the matrix increased. Pilocarpine concentration also decreased in the ungelled cores of the matrices, indicating that the solvent had penetrated these cores. Solvent penetration alone did not control the rate of drug release, because penetration was at least twice as rapid as pilocarpine release. In the matrices without polymer dissolution, the best fits of the release data were obtained with diffusional square-root of time dependence, although relaxation of the polymers caused slight deviations from the Fickian diffusion. Thus the rate-limiting step of pilocarpine release was the diffusion of the drug from the matrix. The decreased rate of pilocarpine release with increased molecular weight and concentration of HPC was due to the decreased rate of drug diffusion from the matrix. Retardation of this diffusion was caused by the increased swelling of the matrix and decreased diffusivity of the drug. High initial concentration of PVP resulted in substantial deformation and attrition of the matrices.