Development of a Model Based on Physical Mechanisms for the Explanation of Drug Release: Application to Diclofenac Release from Polyurethane Films

Abstract

In this study, we present a method for prediction of the drug-release profile based on the physical mechanisms that can intervene in drug release from a drug-carrier. The application presented here incorporates the effects of drug concentration and Reynolds number defining the circulating flow in the testing vein. The experimental data used relate to the release of diclofenac from samples of non-degradable polyurethane subjected to static and continuous flow. This case includes simultaneously three mechanisms: burst-release, diffusion and osmotic pressure, identified beforehand here as being able to contribute to the drug liberation. For this purpose, authors coded the Sequential Quadratic Programming Algorithm to solve the problem of non-linear optimization. The experimental data used to develop the mathematical model obtained from release studies carried out in water solution at 37 °C, for three concentrations of diclofenac and two water flow rates. We discuss the contribution of mechanisms and kinetics by considering two aforementioned parameters and, following that, we obtain the specific-model and compare the calculated results with the experimental results for the reserved cases. The results showed that drug percentage mostly affect the burst release, however flow rate has affected the osmotic release. In addition, release kinetics of all the mechanisms have increased by increasing the values of two considered parameters.