Experimental investigation and mathematical modeling of Pluronic® F127 gel dissolution:: drug release in stirred systems

We have examined the dissolution of Pluronic F127 gels in a USP dissolution apparatus under stirred conditions, and simultaneously monitored the release of model drugs from these gels. The drugs selected were propranolol HCl, metronidazole and cephalexin. Our results show that drug release is zero-order and is controlled by the dissolution of the gel for all the drugs, under various conditions of temperature, F127 concentration, drug concentration, and for stirring speeds between 20 and 80 rpm. The addition of inorganic salts has no significant effect on dissolution rate or drug release. Increasing F127 concentration in the gel decreases gel dissolution and drug release rates. We have developed a predictive mathematical model based on the assumption that uptake of water into the gel and subsequent disentanglement of F127 micelles control gel dissolution. There is good agreement between experimental results and model predictions for stirring speeds above 20 rpm. As stirring speed is decreased to 20 rpm and below, there are discrepancies between actual and predicted values, presumably due to a significant diffusion component that contributes to drug release. (C) 2000 Elsevier Science B.V. All rights reserved.