Biorelevant drug solubility enhancement modeled by a linear solvation energy relationship
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2017
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01A - Journal article
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Journal of Pharmaceutical Sciences
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Volume
107
Issue / Number
1
Pages / Duration
503-506
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Elsevier
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Abstract
It is for the pharmaceutical sciences of vital importance to understand how drugs are solubilized in biorelevant media. However, the complexity of fasted state simulated intestinal fluid (FaSSIF) has so far hampered adequate solubility modeling. The present study focuses on apparently neutral compounds at physiological pH and a linear free energy relationship is introduced for biorelevant drug solubilization. Based on literature data of 40 compounds, the Abraham solvation descriptors were calculated from chemical structure to then predict the ratio of solubility enhancement log(SE) in FaSSIF compared to aqueous buffer solubility at pH 6.5. A suitable model was obtained with R2 of 0.810 and notable were especially the positive effect of McGowan's characteristic volume and the negative effect of drug basicity. A negative influence on log(SE) was further evidenced for dipolarity/polarizability and for the excess molar refraction descriptor. A positive solubilization effect was obtained for drug acidity and hence the tendency for proton donation, which was likely due to the different proton-accepting moieties of taurocholic acid and lecithin that are both present in the mixed colloids of FaSSIF. Overall, an improved understanding was achieved regarding the molecular features that are driving drug solubilization in biorelevant media.
Keywords
solubility, in silico modeling, micelle, oral absorption, phospholipids
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0022-3549
1520-6017
1520-6017
Language
English
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Yes
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Published
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Peer review of the complete publication
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Citation
NIEDERQUELL, Andreas und Martin KUENTZ, 2017. Biorelevant drug solubility enhancement modeled by a linear solvation energy relationship. Journal of Pharmaceutical Sciences. 2017. Bd. 107, Nr. 1, S. 503–506. DOI 10.1016/j.xphs.2017.08.017. Verfügbar unter: http://hdl.handle.net/11654/25769