The Use of Bile Salt Micelles for the Prediction of Human Intestinal Absorption

Laura J. Waters, Dina S. Shokry, Gareth M B Parkes, John C. Mitchell

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

LanguageEnglish
Pages3611-3614
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume105
Issue number12
Early online date21 Oct 2016
DOIs
Publication statusPublished - Dec 2016

Fingerprint

Intestinal Absorption
Micelles
Bile Acids and Salts
Deoxycholic Acid
Pharmaceutical Preparations
Solubility
Linear Models
Spectrum Analysis
Economics
Water

Cite this

@article{1e0f682e8a584e818dc96db9bc6d2c94,
title = "The Use of Bile Salt Micelles for the Prediction of Human Intestinal Absorption",
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.",
keywords = "bile salts, HIA, human intestinal absorption, solubilization, UV",
author = "Waters, {Laura J.} and Shokry, {Dina S.} and Parkes, {Gareth M B} and Mitchell, {John C.}",
year = "2016",
month = "12",
doi = "10.1016/j.xphs.2016.09.007",
language = "English",
volume = "105",
pages = "3611--3614",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "12",

}

The Use of Bile Salt Micelles for the Prediction of Human Intestinal Absorption. / Waters, Laura J.; Shokry, Dina S.; Parkes, Gareth M B; Mitchell, John C.

In: Journal of Pharmaceutical Sciences, Vol. 105, No. 12, 12.2016, p. 3611-3614.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Use of Bile Salt Micelles for the Prediction of Human Intestinal Absorption

AU - Waters, Laura J.

AU - Shokry, Dina S.

AU - Parkes, Gareth M B

AU - Mitchell, John C.

PY - 2016/12

Y1 - 2016/12

N2 - 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.

AB - 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.

KW - bile salts

KW - HIA

KW - human intestinal absorption

KW - solubilization

KW - UV

UR - http://www.scopus.com/inward/record.url?scp=84994509519&partnerID=8YFLogxK

U2 - 10.1016/j.xphs.2016.09.007

DO - 10.1016/j.xphs.2016.09.007

M3 - Article

VL - 105

SP - 3611

EP - 3614

JO - Journal of Pharmaceutical Sciences

T2 - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 12

ER -