DESIGN AND EVALUATION OF OLMESARTAN COCRYSTALS FOR SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT

Abstract

Objective: The present study aimed to enhance the solubility, dissolution rate and oral bioavailability of Olmesartan Medoxomil, a poorly water-soluble antihypertensive agent, through the development of pharmaceutical co-crystals using salicylic acid and benzoic acid as co-formers.

Methods: Co-crystals of Olmesartan were prepared in 1:1 and 1:2 molar ratios using dry grinding (DG), liquid-assisted grinding (LAG) and solvent evaporation (SE) methods. The prepared co-crystals were evaluated for saturation solubility, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), in-vitro dissolution and in-vivo pharmacokinetics.

Results: All co-crystal formulations showed a significant improvement in solubility and dissolution compared to pure Olmesartan. Among them, the optimized formulation OC-S2- SE (Olmesartan : Salicylic acid, 1:2, solvent evaporation) exhibited the highest saturation solubility (0.092 ± 0.012 mg/mL) and drug release (97.86% in 60 minutes). FTIR and DSC confirmed co-crystal formation through characteristic peak shifts and the emergence of a new thermal event at 115.96 °C. SEM analysis revealed a distinct change in surface morphology with uniform and compact crystal aggregates. Pharmacokinetic evaluation showed a significant enhancement in systemic exposure for OC-S2-SE, with a Cmax of 3782 ± 55.42 µg/mL  and  AUC₀–t  of  60405.25 ± 144.84 µg·h/mL,  compared  to

1735 ± 14.56 µg/mL and 28586.50 ± 132.73 µg·h/mL for pure Olmesartan, respectively. Conclusion: Co-crystallization of Olmesartan with salicylic acid, especially via solvent evaporation, is a promising strategy to overcome its solubility and bioavailability limitations. The study validates the potential of pharmaceutical co-crystals to improve the therapeutic efficacy of poorly water-soluble drugs