Improved aqueous solubility and antihypercholesterolemic activity of ezetimibe on formulating with Hydroxypropyl-β-cyclodextrin and hydrophilic auxiliary substances

The purpose of this study was to improve the aqueous solubility, dissolution, and pharmacodynamic properties of a BCS class II drug, ezetimibe (Eze) by preparing ternary cyclodextrin complex systems. We investigated the potential synergistic effect of two novel hydrophilic auxiliary substances, D-αtocopheryl polyethylene glycol 1000 succinate (TPGS) and L-ascorbic acid-2-glucoside (AA2G) on hydroxypropyl-β-cyclodextrin (HPBCD) solubilization of poorly water-soluble hypocholesterolemic drug, Eze. In solution state, the binary and ternary systems were analyzed by phase solubility studies and Job’s plot. The solid complexes prepared by freeze-drying were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and scanning electron microscopy (SEM). The log P values, aqueous solubility, dissolution, and antihypercholesterolemic activity of all systems were studied.

AAPS PharmSciTech, Vol 17, No 2, April 2016 ( # 2015) DOI: 10.1208/s12249-015-0344-7 Research Article Improved Aqueous Solubility and Antihypercholesterolemic Activity of Ezetimibe on Formulating with Hydroxypropyl-β-Cyclodextrin and Hydrophilic Auxiliary Substances Kale Mohana Raghava Srivalli1 and Brahmeshwar Mishra1,2 Received 16 February 2015; accepted 28 May 2015; published online 16 June 2015 Abstract The purpose of this study was to improve the aqueous solubility, dissolution, and pharmacodynamic properties of a BCS class II drug, ezetimibe (Eze) by preparing ternary cyclodextrin complex systems We investigated the potential synergistic effect of two novel hydrophilic auxiliary substances, D-αtocopheryl polyethylene glycol 1000 succinate (TPGS) and L-ascorbic acid-2-glucoside (AA2G) on hydroxypropyl-β-cyclodextrin (HPBCD) solubilization of poorly water-soluble hypocholesterolemic drug, Eze In solution state, the binary and ternary systems were analyzed by phase solubility studies and Job’s plot The solid complexes prepared by freeze-drying were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and scanning electron microscopy (SEM) The log P values, aqueous solubility, dissolution, and antihypercholesterolemic activity of all systems were studied The analytical techniques confirmed the formation of inclusion complexes in the binary and ternary systems HPBCD complexation significantly (pE–CD–AA2G (pE–CD>Eze (p