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

Ulrika Tehler; Jonas H Fagerberg; Richard Svensson; Mats Larhed; Per Artursson; Christel A S Bergström

doi:10.1021/jm301721e

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

Ulrika Tehler, Jonas H Fagerberg, Richard Svensson, Mats Larhed, Per Artursson, Christel A S Bergström

Research output: Contribution to journal › Article › Research › peer-review

46 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2690-2694
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	6
DOIs	https://doi.org/10.1021/jm301721e
Publication status	Published - 28 Mar 2013
Externally published	Yes

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10.1021/jm301721e

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Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice. / Tehler, Ulrika; Fagerberg, Jonas H; Svensson, Richard et al.
In: Journal of Medicinal Chemistry, Vol. 56, No. 6, 28.03.2013, p. 2690-2694.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Tehler, Ulrika

AU - Fagerberg, Jonas H

AU - Svensson, Richard

AU - Larhed, Mats

AU - Artursson, Per

AU - Bergström, Christel A S

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Y1 - 2013/3/28

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AB - 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.

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ER -

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

Abstract

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