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Estimation of the Increase in Solubility of Drugs as a Function of Bile Salt Concentration

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Abstract

Purpose. The objective of this study was to develop a model to predict the extent to which bile salts can enhance the solubility of a drug, based on the physicochemical properties of the compound. The ability to predict bile salt solubilization of poorly soluble drugs would be a key component in determining which drugs will exhibit fed vs. fasted differences in drug absorption.

Methods. A correlation between the logarithm of the octanol/water partition coefficient [log P] of six steroidal compounds and their solubilities in the presence of various concentrations of sodium taurocholate at 37°C, log [SR] = 2.234 + 0.606 log [P] (r2 = 0.987) where SR is the ratio of the solubilization capacity of the bile salt to the solubilization capacity of water for the drug, was used to predict the solubility of five further compounds with diverse structures. The solubilities of the compounds in presence of sodium taurocholate were then measured.

Results. The predicted solubilities were within 10% of the experimentally observed solubilities for griseofulvin, cyclosporin A and pentazocine. The model overpredicted the solubility of phenytoin and diazepam in 15 mM sodium taurocholate solution by a factor of 1.33 and 1.62 respectively.

Conclusions. The expected increase in solubility as a function of bile salt concentration can be estimated on the basis of the partition coefficient and aqueous solubility of the compound.

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Authors and Affiliations

  1. College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, 48109-1065

    Sabena D. Mithani, Vassiliki Bakatselou, Christopher N. TenHoor & Jennifer B. Dressman

  2. Janssen Pharmaceuticals, Athens, Greece

    Vassiliki Bakatselou

  3. Hoechst-Roussel Pharmaceuticals, Somerville, New Jersey, 08801

    Christopher N. TenHoor

  4. Johann Wolfang Goethe-Universitat, Biozentrum, D-60439, Frankfurt am Main, Germany

    Jennifer B. Dressman

Authors
  1. Sabena D. Mithani
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  2. Vassiliki Bakatselou
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  3. Christopher N. TenHoor
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  4. Jennifer B. Dressman
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Mithani, S.D., Bakatselou, V., TenHoor, C.N. et al. Estimation of the Increase in Solubility of Drugs as a Function of Bile Salt Concentration. Pharm Res 13, 163–167 (1996). https://doi.org/10.1023/A:1016062224568

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