¹Department of Pharmaceutics, SVKM NMIMS School of Pharmacy and Technology Management, Shirpur, Dhule, India-425405 DOI : 10.29228/jrp.289 The therapeutic efficacy of an active ingredients are imperfect owing to the poor solubility and dissolution rate. Moreover, dissolution is the rate-limiting period towards the absorption and bioavailability of the active ingredients. Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) recommended for the therapy of high blood pressure as well as minimizes the chances of stroke, heart attack and kidney problems. Olmesartan medoxomil is a BCS class II molecule with only 26 % bioavailability. Hence, the current research work was focused on cost-effective Liquisolid technology for the improvement of solubility, dissolution rate and thereby achieving higher therapeutic efficacy. Liquisolid Compact is one of the best technique for improvement of solubility of potent hydrophobic molecules by utilizing non-volatile solvent. The solubility of olmesartan was estimated in several non-volatile solvents and tween 80 (95 mg/ml) was found to be best. The formed liquid medicaments were converted into the free-flowing powder blends for direct compression by the addition of carrier (Dibasic anhydrous calcium phosphate) and coating agent (Neusilin US2). The drug-excipients compatibilities were confirmed with FTIR. QbD design (Box-Behnken) was applied which comprised of independent factors (X1: DCP, X2: Neusilin US2, X3: CCS) and dependable factors were (Y1: Disintegration time, Y2: Dissolution release). The Design of expert software (DOE, Statease, Version 11) showed 12 batches which were evaluated for their flowing characteristics. The optimized batch F12 showed excellent flowing characteristics (Carr’s index: 14, Angle of repose: 24.42), rapid disintegration time (2.07 min), in-vitro drug release (99.45%) and qualify under accelerated stability testing with minimal drug loss. Keywords : Olmesartan; solubility enhancement; Liquisolid; Box-Behnken design; neusilin US2