Design of supersaturable formulation of telmisartan with pH modifier: in vitro study on dissolution and precipitation

Abstract

Telmisartan is a biopharmaceutics drug classification system class II drug having a low solubility at neutral pH region. The purpose of this study is to clarify the process of dissolution and precipitation of telmisartan in the gastrointestinal tract from its oral formulation containing meglumine, a pH modifier (alkalizer). Granules of telmisartan containing different amount of meglumine were prepared, and its dissolution and precipitation profiles were investigated under various pH conditions in vitro. It was demonstrated that meglumine induced a supersaturation of telmisartan both at pH 5.0 and pH 6.8. Dissolved amount of telmisartan fluctuated over time and the pattern of dissolved concentration differed depending on the pH and the amount of meglumine. Powder X-ray diffraction analysis and differential scanning calorimetry analysis on precipitates from supersaturated solutions showed that pH of the dissolution medium profoundly affects the crystalline form of telmisartan. Furthermore, the effect of meglumine on oral absorption of telmisartan was investigated with dissolution/permeation System in vitro. At pH 6.8, permeated amount was significantly higher with the formulation which contains larger amount of meglumine. Therefore, despite the very low solubility of telmisartan at neutral pH, meglumine significantly provided high solubility of telmisartan by induction and maintenance of its supersaturation.