Pefloxacin (PEF) is an amphoteric, antibacterial drug which exists as a neutral molecule in the crystal structure stabilized by C–H···O and C–H···F interactions. The design of multicomponent solids using crystal engineering was undertaken in a cocrystal / salt screen of PEF with GRAS dicarboxylic acids to improve the solubility and phase stability of the drug. Ten multicomponent forms, namely five salts, two salt hydrates, and three salt-cocrystals were crystallized by liquidassisted grinding followed by crystallization. In some cases, salt and salt-cocrystals were obtained concomitantly during solution evaporative crystallization. Single crystal X-ray diffraction showed that the structures are stabilized by N⁺ –H···O^– , O–H···O, C–H···O, C–H···F and π- π stacking interactions. The bulk phase purity of multicomponent forms was characterized by powder X-ray diffraction, spectroscopy and thermal techniques. The salt /salt-cocrystal forms exhibit faster dissolution rate and higher solubility compared to pure PEF in pH 1.2 (acidic, like gastric environment) and pH 7 phosphate buffer media (neutral, like intestinal passage). Specifically, PEF+ -SA– salt showed remarkably high solubility, dissolution rate and stability compared to the other multicomponent forms and PEF neutral form. The drug formulation compatible pefloxacin succinate is a promising soluble and stable PEF salt.

Authors: Anilkumar Gunnam†, Kuthuru Suresh†, and Ashwini Nangia*

¹School of Chemistry, University of Hyderabad, Hyderabad 500 046, India

²Council of Scientific and Industrial Research National Chemical Laboratory, Pune       411 008, India

 *Correspondence e-mail: ashwini.nangia@gmail.com

 Publication date : March 26^th, 2018