Norfloxacin-CO2 crystal formed under supercritical CO2 and enhanced Norfloxacin dissolution properties

Abstract

A molecular crystal of Norfloxacin coupled with CO2, was produced after the supercritical CO2 treatment of Norfloxacin form B. The effects of pressure and temperature on Norfloxacin-CO2 crystal formation are studied semi-quantitatively using on powder XRD and TGA. The higher pressure and temperature conditions result in the formation of more Norfloxacin-CO2 crystals for a limited time. Based on these results, pure Norfloxacin-CO2 crystals are fabricated. Through further studies, we found out that CO2 is fixed in Norfloxacin-CO2 crystal through the formation of a paired carbamic acid structure with two piperazine groups from two adjacent Norfloxacin molecules. The fixed CO2 can be released during dissolution, improving the equilibrium solubility of Norfloxacin from 0.28 mg g−1 water to 0.64 mg g−1 water at 25 ºC. Since no toxic organic solvent used, this research offers a new pathway for greener and safer enhancement for the dissolution properties of poorly soluble APIs.