Controlled drug release from Gelucire-based matrix pellets: Experiment and theory

Abstract

The aim of this work was to elucidate the underlying drug release mechanisms from lipidic matrix pellets, using theophylline and Gelucire 50/02 as model drug and carrier material, respectively. Pellets were prepared by two different techniques: melt-solidification and extrusion-spheronization. The effects of different formulations and processing parameters on the resulting drug release kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained results analyzed using adequate mathematical models in order to get further insight into the underlying mass transport mechanisms. The type of preparation technique was found to strongly affect the underlying drug release mechanisms. Drug release from pellets prepared by the melt-solidification method was primarily controlled by pure diffusion, whereas drug release from pellets prepared by the extrusion-spheronization method was purely diffusion-controlled only at early time points. After approximately 2 h, the pellets started to disintegrate, resulting in decreased diffusion pathway lengths and, thus, increased drug release rates. Furthermore, the curing conditions significantly affected the theophylline release kinetics, whereas varying the initial drug loading from 20 to 50% (w/w) resulted only in a slight increase in the relative drug release rate. Interestingly, the effects of the size of pellets prepared by the melt-solidification method on the resulting drug release kinetics could be quantitatively predicted using an analytical solution of Fick's second law of diffusion. These predictions could be verified by independent experiments.