MODIFICATION OF MICROENVIRONMENTAL PH AS AN APPROACH FOR IMPROVING VALSARTAN DISSOLUTION RATE FROM DRUG-POLYMER SOLID DISPERSIONS

Abstract

This study investigated potential using of valsartan ternary solid dispersions containing hydrophilic polymer and alkalizer in order to improve valsartan dissolution rate in an acidic medium. Valsartan was selected as a model drug due to its low solubility at low pH and presence of absorption window in the upper part of gastrointestinal tract, which altogether causes its low bioavailability after peroral administration. Polyvinylpyrrolidone and hypromellose were used as components of solid dispersion polymeric matrix, while magnesium oxide, calcium oxide, meglumine and sodium carbonate were evaluated as alkalizers. Slow and incomplete valsartan release was achieved from binary solid dispersions, while all tested alkalizers to certain degree led to increase of microenvironmental pH and improvement of valsartan dissolution rate. Formulations containing valsartan, polyvinylpyrrolidone and sodium carbonate (drug:polymer alkalizer ratios 1:2:1 and 1:2:2) and valsartan, polyvinylpyrrolidone and calcium oxide (drug:polymer alkalizer ratio 1:2:1) exhibited fast and immediate valsartan release, with more than 80% of dissolved drug after 30 minutes of testing.