Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice

…, M Larhed, P Artursson, CAS Bergström

Index: Tehler, Ulrika; Fagerberg, Jonas H.; Svensson, Richard; Larhed, Mats; Artursson, Per; Bergstroem, Christel A. S. Journal of Medicinal Chemistry, 2013 , vol. 56, # 6 p. 2690 - 2694

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Citation Number: 11

Abstract

Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural ...