Abstract
Micellar liquid chromatography is a popular method used in the determination of a compound's lipophilicity. This study describes the use of the obtained micelle–water partition coefficient (log P mw) by such a method in the prediction of human intestinal absorption (HIA). As a result of the close resemblance of the novel composition of the micellar mobile phase to that of physiological intestinal fluid, prediction was deemed to be highly successful. The unique micellar mobile phase consisted of a mixed micellar mixture of lecithin and six bile salts, i.e. a composition matching that found in the human intestinal environment, prepared in ratios resembling those in the intestine. This is considered to be the first method to use a physiological mixture of biosurfactants in the prediction of HIA. As a result, a mathematical model with high predictive ability (R 2 PRED = 81%) was obtained using multiple linear regression. The micelle–water partition coefficient (log P mw) obtained from micellar liquid chromatography was found to be a successful tool for prediction where the final optimum model included log P mw and polar surface area as key descriptors with high statistical significance for the prediction of HIA. This can be attributed to the nature of the mobile phase used in this study which contains the lecithin–bile salt complex, thus forming a bilayer system and therefore mimicking absorption across the intestinal membrane.
Highlights
The oral route is the most popular route of administration for pharmaceutical entities
A 17 mM stock solution of a mixed micellar system was prepared by transferring accurately weighed amounts equivalent to 2.71, 2.00, 2.08, 2.08, 4.70 and 3.43 mM of sodium taurocholate (NaTC), sodium taurodeoxycholate (NaTDC), sodium deoxycholate (NaDC), NaC, NaGC and NaGDC bile salts respectively and 0.75 mM of egg phosphatidylcholine to a 250 mL volumetric flask with buffer solution (10 mM HEPES, pH 6.5) in 0.15 M NaCl
Following analysis of a group of 18 model drugs using a physiologically simulating bile salt–lecithin mixed micellar solution, followed by calculation of log Pmw from the calibration plots of 1/k′ against CM, the obtained log Pmw and a number of other molecular descriptors such as molecular weight, polar surface area (PSA), freely rotating bonds, molar volume, dissociation constant, aqueous solubility, number of hydrogen bond donors and number of hydrogen bond acceptors were used for developing a model for prediction of %human intestinal absorption (HIA)
Summary
The oral route is the most popular route of administration for pharmaceutical entities. A very important physicochemical property indicating lipophilicity, log Pmw, can be obtained using MLC in the presence of different surfactants as the micellar mobile phase to help characterize compounds (Kawczak et al, 2010; Marina & Garcia, 2000). A 17 mM stock solution of a mixed micellar system was prepared by transferring accurately weighed amounts equivalent to 2.71, 2.00, 2.08, 2.08, 4.70 and 3.43 mM of NaTC, NaTDC, NaDC, NaC, NaGC and NaGDC bile salts respectively and 0.75 mM of egg phosphatidylcholine to a 250 mL volumetric flask with buffer solution (10 mM HEPES, pH 6.5) in 0.15 M NaCl. The solution was sonicated for 30 min and stored for 12 h before use to allow the formation of stable mixed micelles. The partition coefficient (log Pmw) was obtained from the slope and intercept of the line obtained from the plot of (CM) against (1/k′): log Pmw 1⁄4 log1⁄2intercept=slope
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
