STRUCTURE AND BEHAVIOR IN HYDROPHILIC MATRIX SUSTAINED-RELEASE DOSAGEFORMS .3. THE INFLUENCE OF PH ON THE SUSTAINED-RELEASE PERFORMANCE AND INTERNAL GEL STRUCTURE OF SODIUM ALGINATE MATRICES

The effect of pH and drug solubility on the release kinetics of sodium alginate matrices has been studied. Release of a highly soluble model drug, chlorpheniramine maleate, was significantly faster in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF), whereas the opposite effect was observed for hydrochlorothiazide, a drug of p oor solubility. These results could be explained in terms of the inter nal microscopic structure of the hydrated surface layer formed on matr ix hydration and by the different hydration kinetics of the polymer in these two media. Cryogenic electron microscopy revealed the hydrated surface layer formed by alginate matrices in SGF to be particulate and porous in nature, in contrast to the highly hydrated continuous gel l ayer formed in SIF. Drug release mechanisms were discussed with respec t to drug solubility and the structure and properties of the surface l ayers formed by alginate matrices when hydrated in different pH media.