Effects of the method of drug incorporation and the size of the monolith on drug release from cross-linked polymers

Abstract

Poly(vinyl alcohol) was cross-linked by glutaraldehyde to form a water-swellable polymer possessing a three-dimensional molecular network. The glassy polymeric material was loaded with proxyphylline, used as a model drug, and shaped into two geometrically different types of monolithic devices, i.e. micromatrices and monolithic slabs. In the case of the micromatrices, the drug was incorporated either during the cross-linking reaction by dissolving it in the reaction solution or after cross-linking by a soaking technique. For the slabs, drug loading was performed only by the soaking method. The polymer network structure was characterized by equilibrium swelling measurement which allowed the determination of the average distance between cross-links. Drug release from the micromatrices loaded during cross-linking could be controlled over more than 8 h if the cross-linking density of the polymeric substrate was high. In these dense networks, the type of release appeared to be diffusion-controlled. In addition to the cross-linking density, the particle size greatly influenced the delivery rate. In contrast, the micromatrices loaded by the soaking method released the drug in less than 20 min. The monolithic slabs, drug-loaded by the soaking method, showed the most interesting release behaviour. After 8 h, only 40–60% of proxyphylline was released although the slabs contained up to 51% of this highly water-soluble compound. Moreover, drug release was found to be controlled not only by the solute diffusion but also by the polymer swelling process.