(302b) A Multicomponent Transport Model of Drug Release from Hydrophilic Polymer Matrix Tablets

Polymeric matrices are key components in controlled drug release devices for solid oral delivery. We propose a 1D transport model of drug release from hydrophilic matrices. Water induced matrix stress is integrated into the total mixing free energy so that matrix stress contributes directly to diffusion driving force while leading to time-dependent boundary conditions at tablet interface. Given that hydrated matrix tablets are dense multicomponent systems, extended Stefan-Maxwell (ESM) flux laws are adopted in this work to ensure consistency with Onsager reciprocity principle and Gibbs-Duhem thermodynamic constraint. An ESM flux law for any given component takes into account the diffusional friction exerted by all other species and is invariant with respect to reference velocity. Our model demonstrates that penetrant induced plasticization of polymer chains partially or even entirely offsets the steady decline of chemical potential gradients at tablet-medium interface that drive drug release. Utilizing Flory-Huggins thermodynamic model, a modified form of upper convected Maxwell constitutive equation and Fujita-type dependence of mutual diffusivities on composition, Fickian, anomalous and case II drug transport are obtained which are characterized by power law release profiles with exponents ranging from 0.5 to 1, respectively. A necessary requirement for non-Fickian release in our model is that matrix stress relaxation time is comparable to water diffusion time scale. Mutual diffusivities and their composition dependence are the most decisive factors in controlling drug release characteristics in our model. The model predictions are also compared to representative experimental data.