In Vitro Drug Release Rates From Asymmetric-Membrane Tablet Coatings: Prediction of Phase-Inversion Dynamics

Abstract

Most of the controlled-release systems developed for drug delivery applications depend on membrane technology. The dense structure of some membranes used in controlled-release systems can excessively prolong the release of drug due to the low permeability of the coating to drug. To increase the drug release rate, asymmetric-membrane tablet coatings were prepared by a phase-inversion technique using cellulose acetate/acetone/water solution. The roles of the composition of the membrane solution and the evaporation condition on the release rate of drug were determined using in vitro dissolution and morphological studies and predicted phase diagrams. Results show that drug release from asymmetric-membrane based tablet coatings is primarily governed by the dynamics of the phase-inversion process with zero-order or near-zero-order release easily achievable. In an attempt to derive an empirical expression for the release rate of drug as a function of composition of the coating solution, a statistical experimental design was used. Good fit of the experimental data by the empirical expression was obtained. In addition, the predictive capability of the model equation was also found to be satisfactory. Analysis of the significance of each term in the expression indicates that the cellulose acetate:acetone ratio has the most significant influence on the release rate of theophylline.