Mechanochemical solid-state polymerization. IX. Theoretical analysis of rate of drug release from powdered polymeric...

We theoretically derived the rate equation of drug release from a simple model in a heterogeneous system. Four assumptions were used to simplify the model. Two kinds of rate equations for drug release derived from two possible limiting cases, that the rate-determining step is a diffusion or hydrolysis controlled process, can predict the experimental results up to 50% hydrolysis. However, the predictions at the later stage by these equations are insufficient. These results suggest that the process of drug release from powdered polymeric prodrugs in a heterogeneous system must be described by both diffusion and hydrolysis. The rate equation derived from a model considering both the diffusion and hydrolysis processes can successfully predict the experimental results for several kinds of polymeric prodrugs. It is also shown that the diffusion coefficient and rate constant for hydrolysis calculated from this equation thoroughly express the character of the comonomer. The rate equation derived from the model that considers both diffusion and hydrolysis is very useful to analyze drug release from various kinds of polymeric prodrugs in a heterogeneous system.