Investigations on solid dispersions of valsartan with alkalizing agents: Preparation, characterization and physicochemical properties

Valsartan has been used for the treatment of hypertension disease. However, the oral bioavailability of valsartan has been reported to be only ∼23%, accompanied with high permeability and poor aqueous solubility. The object of this research was to prepare solid dispersions of valsartan with an inorganic (CaCO3) and organic base (N-methyl-d-glucamine) in an effort to increase the aqueous solubility and dissolution rate of the drug. The as-prepared solid dispersions of valsartan were prepared in an environmentally friendly manner using CaCO3 and MG and a roll mill. The physicochemical properties were studied in the solid state using DSC, PXRD and IR. Furthermore, the solubility of valsartan increased 46-fold in solid dispersion with CaCO3 and 9-fold in solid dispersion with MG. More than 95% of valsartan in solid dispersions was found to be released in simulated intestinal fluid, whereas only 35% was found to be released using pure valsartan within the same time interval. Storage tests showed that the as-prepared solid dispersions were equally stable compared to pure valsartan at 40 °C. Potentially, the synthesized solid dispersions of valsartan with enhanced solubility and dissolution rates may represent promising formulations for improving the overall oral bioavailability of the drug in clinical applications.