Mechanisms of diphylline release from dual-solute loaded poly(vinyl alcohol) matrices

The release kinetics of the model hydrophilic drug, diphylline (DPL), from physically crosslinked poly(vinyl alcohol) (PVA) matrices, is studied in relation to the drug load and the presence of a second solute incorporated in the matrix. The second solute, a gadolinium (III) complex (Gd-DTPA), is a commonly used MRI contrast agent. The water uptake kinetics by the glassy PVA matrix was found to deviate from t1/2 law and to occur on time scales comparable to those of diphylline release. The corresponding rate of diphylline release was found to be substantially stabilized as compared to a purely diffusion-controlled release process, in line with theoretical predictions under conditions of relaxation-controlled water uptake kinetics. The release rate of DPL was found (i) to increase with increasing DPL load and (ii) for a particular DPL load, to increase in the presence of Gd-DTPA, incorporated in the matrix. The results were interpreted on the basis of the diphylline-induced plasticization of the polymer (evidenced by the depression of Tg) and of the excess hydration of the matrix at high solute loads. The latter effect was found to be additive in the case of dual-solute loaded matrices.