Formulation, in-vitro evaluation and optimization of valsartan nano-lipid complex by Box-Behnken design

The antihypertensive drug valsartan, has an imperfect bioavailability due to its low solubility, permeability and excessive first pass hepatic metabolism. So, the goal of this article is to improve the physicochemical properties of valsartan to increase its bioavailability. In order to achieve this goal, valsartan- phospholipid complexsomes (VAL-PLC) were developed by the technique of solvent evaporation using Box-Behnken experimental design to optimize variables in the production process. The box- Behnken design revealed that the formula F3 prepared using 60% lipid percentage at 60⁰C reaction temperature for 2h reaction time offered the optimum conditions for VAL-PLC preparation where the percent drug content reached 92.24%, average particle diameter was 189.17nm and polydispersity index was 0.289. Drug release experiment indicated that the dissolution of both raw valsartan and its commercial dosage form was dependent upon pH where it was extremely low at pH 1.2 and low in distilled water and it had a high dissolution at pH 6.8. On the contrary, the optimized VAL-PLC formula showed a high and pH-independent dissolution rate whatever the type of dissolution medium was. Therefore, it was concluded that valsartan-complexsomes may be considered as an encouraging approach for improving physicochemical properties and increasing bioavailability of valsartan.