title: Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice.
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 changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.
authors: Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden.
authors: Ulrika
authors: U
authors: Tehler
authors: Jonas H
authors: JH
authors: Fagerberg
authors: Richard
authors: R
authors: Svensson
authors: Mats
authors: M
authors: Larhed
authors: Per
authors: P
authors: Artursson
authors: Christel A S
authors: CA
authors: Bergström
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D018938:Caco-2 Cells; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010539:Permeability; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents