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 asymmetricmembrane 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.
Asymmetric membranes were prepared by dry-cast phase inversion technique from a cellulose acetate, acetone, water solution in order to assess the validity of the mathematical model recently developed by us. Based on the model predictions, general structural characteristics of the membranes were determined by plotting the composition paths on the ternary phase diagram and polymer concentration profile at the first moment of precipitation. Composition paths on the ternary phase diagram enable the assessment of whether a phase separation occurs and allow prediction of inception time and duration of the phase separation. The polymer distribution at the moment of precipitation provides a rough thickness of the high polymer concentration region near the interface and a pore distribution of the sublayer structure. The effects of polymer/nonsolvent ratio in the casting solution, the initial film thickness, evaporation temperature, relative humidity and velocity of air were investigated. Model predictions were compared with the morphological analysis conducted using scanning electron microscopy. Results show that diffusion formulation plays an important role in capturing the accurate structure of the membrane from the model predictions.
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