Open AccessOptimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug Using Lipophilic Fragments Disturbing the Crystal Lattice
Author(s) -
Ulrika Tehler,
Jonas H Fagerberg,
Richard Svensson,
Mats Larhed,
Per Artursson,
Christel A S Bergström
Publication year - 2013
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/jm301721e
Subject(s) - biopharmaceutics classification system , solubility , chemistry , lipophilicity , biopharmaceutics , melting point , permeability (electromagnetism) , chromatography , organic chemistry , biochemistry , pharmacognosy , in vitro , membrane , biological activity
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 changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.