Abstract

Solubility of the active ingredient in the body is the key factor associated with their therapeutic efficacy, in vitro and in vivo correlations. Approximately 90 % of the newly developed active ingredients and 40 % of existing molecules suffered from poor solubility properties and thereby significantly affecting the solubility in the gastrointestinal tract resulted in poor bioavailability. The current aim of the research article is to provide higher bioavailability of ambrisentan by improving its solubility and dissolution rate. Ambrisentan is an endothelin receptor antagonist useful in the treatment of pulmonary arterial hypertension. The solubility of ambrisentan was enhanced by the liquisolid technique using several non-volatile solvents and polyethylene glycol 400 (0.828 mg/ml) was found to be best. The varying concentration of carriers (microcrystalline cellulose, dibasic calcium phosphate) and Aerosil 200 as coating agents was added to develop tablets. The physical interaction study of ambrisentan with non-volatile solvent, carrier and coating agents were performed. The powder blends were evaluated for flow characteristics (Carr’s index and angle of repose). A powder with good flowing characteristics was subjected to tablet manufacturing and evaluated further. The optimization was carried out with Box-Behnken design which provided 32 designs. The carrier, coating agent and superdisintegrants were selected as independent parameters and disintegration and dissolution time as dependent parameters. The optimized batch F2 showed with least disintegration time of 2.12 min and the highest percentage of drug dissolution was 99.61 % within 30 min. Hence, the F2 batch was short-listed and successfully passes the stability testing.