Anomalous release of hydrophilic drugs from poly(epsilon-caprolactone) matrices.

In this paper, we investigate the release of two drugs, nicotine and caffeine, from poly epsilon-caprolactone (PCL) matrices, as a model for the delivery of highly hydrophilic drugs. Since PCL does not degrade over the period of our experiments (<30 days), drug diffusion through the matrix is expected to be the dominant mechanism of release. Contrary to expectations, we find that the drug diffusion coefficient increases with increasing drug loading, weakly for caffeine and strongly for nicotine. The water content in the PCL matrices (after all of the drug was released) was found to be orders of magnitude higher than the expected value, increasing with increasing drug loading. We suggest that these phenomena arise from the semicrystalline nature of PCL under our experimental conditions, which inhibits matrix collapse when the drug is released, thereby creating voids into which water can diffuse. We apply a quantitative model for these systems that considers counter-diffusion of water into the matrix with drug diffusion out of the matrix. The high solubility of both drugs in aqueous solutions leads to drug partitioning into the polymer-encapsulated water, thereby increasing the effective rate of drug diffusion and release. The model is shown to fit the experimental data of both drugs using only one fit parameter.