Mechanistic studies of macromolecular drug release from macroporous polymers. I. Experiments and preliminary theory concerning completeness of drug release

The release of the model polypeptide drug bovine serum albumin (BSA) from macroporous ethylene-vinyl acetate copolymer matrices has been investigated over a wide range of drug loadings and particle sizes. At low drug loadings a fraction of the drug is released relatively quickly from the matrix surface, but the remainder of the drug is virtually trapped within the matrix and is released at an extremely slaw rate. At high drug loadings all drug is released. A simple model of drug trapping, based on a modification to percolation theory, is proposed. The model predictions are qualitatively in agreement with the data, but are unable to predict certain quantitative features. It is suggested that the discrepancies are due to a nonuniform distribution of drug in the matrices, which is shown to exist by scanning electron microscopy.