Design of silica carrier for controlled release of molsidomine: effect of preparation methods of silica matrixes and their composites with molsidomine on the drug release kinetics in vitro.

Biodegradable, controlled-release carrier materials with non-toxic degradation products are very valuable for delivery of cardiovascular drugs. This study is a part of development of novel form of vasodilator molsidomine to improve pharmacokinetic and consumer properties of the drug. It focuses on the effect of preparation methods of the drug-silica composites on their release kinetics. Phenyl modified silica materials prepared by different ways were studied as potential carriers for molsidomine. The composites of molsidomine with the modified silica were synthesized via one-step sol-gel route and adsorption. The drug was adsorbed onto the phenyl modified silica prepared by co-condensation and grafting. Furthermore, the one-step sol-gel derived composites were prepared at pH 4.4 (the isoelectric point of the drug) and pH 6.3 (the zero point of charge of the silica). In vitro release kinetics of molsidomine from the synthesized composites in simulated gastric (pH 1.6) and simulated blood (pH 7.4) media was studied. Our findings demonstrate that the release of the drug can be controlled by manipulating the synthesis ways and changing the sol-gel pH. The comparative analysis of molsidomine release profiles from the composites prepared by one-step sol-gel synthesis at different pH and adsorption allows to reveal perspective composites which exhibit sustained release of molsidomine for about 36h in acidic medium close to the zero order release kinetics.