Examination of the solubilization of drugs by bile salt micelles.

The purpose of this review is to provide a critical examination of the reported solubilization of drugs by bile salt micelles. The underlying premise is that with better information regarding the inherent biological complexity, efforts to predict the oral bioavailability of drug will be enhanced. The common means of comparing the reported values was chosen to be the solubilization ratio. This is equal to the moles of drug solubilized per mole of bile salt. The values were segregated according to bile salt type, temperature, ionic strength, and the presence and absence of added lipids. Only segregation by bile salt type was pairwise statistically significant. From the solubilization ratios and the reported values of the aqueous solubility, the logarithms of the mole fraction micelle partition coefficients, log K(m/a), were calculated. The log K(m/w) was found to be correlated with the reported logarithm of the octanol/water partition coefficient. The rank order of slopes of the log K(m/a) as a function of log K(o/w) was cholate approximately taurodeoxycholate > glycocholate approximately taurocholate approximately glycodeoxycholate, with deoxycholate not being statistically different from the other data sets. The slope and intercept for the bile salt mixed micelle systems were 0.600 and 2.44, respectively, which were statistically indistinguishable from glycocholate, taurocholate, and glycodeoxycholate bile salt data. The existence of statistically significant correlations suggests that predicting the solubilization in the intestine may be possible with in vitro measurements if additional information is gathered in the appropriate micellar solutions. Copyright 2002 Wiley-Liss Inc. and the American Pharmaceutical Association