Waters, Laura J., Shokry, Dina S., Parkes, Gareth M. B. and Mitchell, John C. ORCID: https://orcid.org/0000-0003-2945-3292 (2016) The use of bile salt micelles for the prediction of human intestinal absorption. Journal of Pharmaceutical Sciences, 105 (12). pp. 3611-3614. ISSN 0022-3549 (Print), 1520-6017 (Online) (doi:10.1016/j.xphs.2016.09.007)

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Abstract

Human intestinal absorption (HIA) will dictate biopharmaceutical performance through its influence on absorption, distribution, metabolism, and elimination and can vary significantly depending upon the nature of the compound under consideration. In this study, an in vitro assay method is proposed for the prediction of HIA through the measurement of drug solubility in an aqueous phase containing micellar bile salt, namely sodium deoxycholate. A series of twenty compounds, displaying a range of physicochemical properties and known HIA values, were analyzed using UV spectroscopy to determine a solubilization ratio for each compound. A micelle/water partition coefficient (Kxm/a) was calculated and then used to develop an equation through simple linear regression; logit HIA = −0.919 + 0.4618 logKxm/a (R2 = 0.85). From this equation, a value for % HIA was determined which compared well with literature. Furthermore, 4 additional drugs were then analyzed using the developed equation and found to match well with literature, confirming the suitability of the method. Using a simple, economic, and robust UV bile salt assay allows prediction of HIA and avoids many of the disadvantages of other techniques, such as animal-based methods.

Item Type:	Article
Additional Information:	© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords:	Human intestinal absorption (HIA), absorption, bile salt,sodium deoxycholate.
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	08 Apr 2020 12:51
URI:	http://gala.gre.ac.uk/id/eprint/15911

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