THE BINARY AND TERNARY AMORPHOUS SYSTEMS OF CANDESARTAN CILEXETIL PREPARATION TO IMPROVE ITS SOLUBILITY

Abstract

Objective: The objectives of this work was to prepare the binary and ternary amorphous systems of Candesartan cilextil (CAN), characterize these, and evaluate their influence on solubility. Methods: CAN was prepared in three amorphous systems, namely Candesartan cilexetil-l-Arginine (CAN-ARG) binary Co-Amorphous System (CAMS), CAN with 10, 20, and 30% of Polyvinylpyrrolidone K25 (CAN-PVP K25) Amorphous Solid Dispersion (ASD), and CAN-ARG with 10, 20, and 30% of PVP K25 (CAN-ARG-PVP K25) ternary CAMS. All amorphous systems were characterized by polarizing microscopy and differential scanning calorimetry (DSC) methods, while the degree of crystallinity was calculated based on powder X-ray diffraction (PXRD) patterns. The solubility test of all amorphous systems of CAN was carried out respectively in water solvent (25±0.5 °C) and phosphate buffer solution with a pH of 6.5 that contained 0.70% polysorbate 20 at 37±0.5 °C. Results: Polarization microscope images showed no birefringence in CAN-ARG and CAN-ARG-PVP K25 CAMS, but strong birefringence in CAN-PVP K25. DSC thermograms show the glass transition of CAN-ARG-PVP-K25 was in the range 101-120.8 °C higher than CAN-PVP-K25 (84.1-87.5 °C) and CAN-ARG (53.5 °C). The crystallinity degrees of CAN, CAN-ARG, CAN-PVP K25, and CAN-ARG-PVPK25 calculated based on powder X-ray diffractogram data were 73.68, 7.52, 17.20, and 0.02%, respectively. The order of solubility of CAN in water and phosphate buffer solution with a pH of 6.5 that contains 0.70% polysorbate 20 was CAN-ARG-PVP-K25>CAN-ARG>CAN-PVP-K25>CAN. Conclusion: The synthesis of binary and ternary amorphous CAN has resulted in positive outcomes, enhancing its solubility.