DIFFERENTIAL SCANNING CALORIMETRY ANALYSIS, EQUILIBRIUM SOLUTION AND LIPID-WATER PARTITION COEFFICIENT OF O-19, A PROMISING PRODRUG CANDIDATE OF O-DESMETHYLVENLAFAXINE

Zihao Zhang, Guiyong Wang, Zhongyu Zhang, Yang Zhang

ABSTRACT:Compound O-19 is a promising prodrug candidate of O-desmethylvenlafaxine (ODV) with excellent oral bioavailability and improved brain uptake. In present investigation, with the aim to gain the information on druggability of O-19, the DSC analysis and physicochemical properties including solubility (S), lipid/water partition coefficient (Log P) coupled with solid state stability evaluation were performed and compared with ODV. Results indicated that O-19 showed unique double peaks associated with the crystal transition during differential scanning calorimeter (DSC) processing as well as excellent stable properties during storage in room temperature. Its solubility and Log P exhibited similar trends towards ODV and mainly influenced by the countered pH environment. Herein, this work would be helpful for the further development of O-19 as a novel antidepressant drug.

Keywords:Compound O-19, DSC analysis, solubility, Log P