Modeling of drug release, erosion and diffusion fronts movement in high viscosity HPMC matrices containing a cellulolytic enzyme

Abstract

A formerly developed mathematical model describing drug release from hydrophilic matrices (HMs) took into account resistance to drug release given by its dissolution and by the presence of a growing gel layer. Such a model was applied to previously reported release data obtained from HMs made of hydroxypropyl methylcellulose (HPMC), where acetaminophen was used as model drug and a cellulolytic product was added as “active” excipient to attain zero-order release kinetics. The Levich theory applied to acetaminophen intrinsic dissolution rate (IDR) data highlighted the suitability of such a drug for modeling purposes, given its good surface wettability. First assessment of the model ability to describe drug release from the abovementioned systems was carried out on partially coated matrices, representing a simplified physical frame, but results were then confirmed on uncoated systems. Experimental and model release data showed good agreement; therefore, the release-describing equation was combined with that of the global mass balance to obtain two new equations related to erosion and diffusion fronts time evolution. Changes over time in the dissolution and gel contributions to total resistance, calculated using model output parameters, highlighted that the enzyme, through its hydrolytic activity on HPMC, was responsible for a time-dependent reduction of the resistance component related to gel layer.