EVALUATION OF A SILICONE-BASED MATRIX CONTAINING A CROSS-LINKED POLYETHYLENE-GLYCOL AS A CONTROLLED DRUG-DELIVERY SYSTEM FOR POTENTIAL ORAL APPLICATION

A silicone based matrix containing dispersed medicated granules of a crosslinked polyethylene glycol with high swelling capacity is evaluated for its potential to release in vitro substantial fractions of drugs of different solubilities within 6 hours at controlled rates. Papaverine . HCl, clonidine . HCl and salicylamide are the model drugs. With a matrix shape of a 0.1-cm thick disc, a weight fraction of granules in matrix of around 35% and an appropriate granule size, dose fractions of around 80% are released with root t-type kinetics. The particular drug type and the drug content in granules, within the range of 5-20%, are without influence on the pattern and rate of fractional release. The release pattern depends on the pH of the elution medium, but the pH effects can be offset by properly controlling the granule size. Thus, the above features of release are obtained with normal saline as the elution medium, using granules of 354-425 mu m, or with a medium whose pH is gradually increased from 1.2 to 7.4 to simulate the conditions of the GI tract, using granules of 105-250 mu m. Drug release is initially controlled by the rate of increase of the number and size of interconnections among granules in course of swelling. Drug diffusion in the interconnected hydrogel gradually takes control of release.