Controlled Drug Release from Polymeric Delivery Devices II: Differentiation Between Partition-Controlled and Matrix-Controlled Drug Release Mechanisms

Abstract

The drug release pattern of micronized ethynodiol diacetate from silicone devices was thoroughly investigated in polyethylene glycol-containing elution media with a wide range of solubility and partition properties. When high drug solubility was maintained, the drug release pattern followed a Q - t1/2 relationship (matrix controlled). Under this matrix-controlled process, the drug release profiles were independent of the variation in partition coefficient magnitude and insensitive to the change in solubility parameters. As the drug solubility in the elution medium was decreased, the drug release process shifted from matrix controlled to partition controlled, and a Q - t (zero-order) relationship was observed. The drug release profile was then a function of the partition coefficient of drug from the polymer matrix to the elution medium. A transition phase was also seen between these two processes. Matrix-controlled and partition-controlled drug release processes were analyzed theoretically. The experimental rates of drug release were in perfect agreement with the values calculated from the theoretical model.