Synthesis and evaluation of valsartan co-crystals for enhanced solubility and anti-hypertensive activity

Valsartan (VAL) is an antihypertensive medication belonging to the angiotensin II receptor blockers class, which helps reduce cardiovascular disease risk by controlling high blood pressure, but its therapeutic efficacy is limited due to poor solubility and bioavailability. The study focused on developing valsartan cocrystals using co-formers through the solvent evaporation method to improve the solubility and thereby efficacy of VAL. The cocrystal formulation was optimized using a central composite design to achieve the critical quality attributes of cocrystals. Optimized formulation was characterized by using various physiochemical analyses including X-ray diffraction, which confirmed the crystallinity, and Scanning Electron Microscopy showed rough, irregular surface morphology. The drug content in the optimized formulation was ∼77 % for valsartan-saccharin co-crystals (VAL-SAC) and ∼74 % for valsartan-glutaric acid cocrystals (VAL-GUL). In-vitro release profiles displayed an initial burst followed by sustained release. VAL-SAC cocrystals showed aqueous solubility of 0.7710 ± 0.012 mg/mL while VAL-GUL cocrystals exhibited solubility of 0.2740 ± 0.018 mg/ml which is notable than plain drug (0.0201 ± 0.001 mg/mL). In-vivo results indicated that the cocrystal formulations of VAL had better antihypertensive efficacy than the plain drug alone. These results highlight the potential of the developed cocrystals as effective antihypertensive agents.