Enhancing Solubility of Candesartan Cilexetil by Co-milling; Preparation of Candesartan Cilexetil-glycyrrhizic Acid Composite
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No.18 Chaowang Road, Hangzhou 310014, China
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No.18 Chaowang Road, Hangzhou 310014, China, E-mail: [email protected]
Candesartan cilexetil was complexed with glycyrrhizic acid to enhance its aqueous solubility. Solid dispersion of candesartan cilexetil and glycyrrhizic acid were prepared by mechanochemical technique of milling at 120 rpm for 8 h. This solid dispersion could significantly improve the solubility of candesartan cilexetil in water. In vitro drug release showed a significant increase in drug dissolution rate after formation of a solid dispersion with glycyrrhizic acid. It was also found that the chemical stability of the solid dispersions was enhanced compared to pure candesartan cilexetil in a stability study involving heat, light, and long-term storage. The results of differential scanning calorimetry, X-ray powder diffraction shown that the drug existed in the amorphous state. Fourier-transform infrared spectra demonstrated that hydrogen bonding occurred between candesartan cilexetil and glycyrrhizic acid with mechanical and chemical treatment.