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 Km/a, were calculated. The log Km/w was found to be correlated with the reported logarithm of the octanol/water partition coefficient. The rank order of slopes of the log Km/a as a function of log Ko/w was cholate ≈ taurodeoxycholate > glycocholate ≈ taurocholate ≈ 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.
Bibliographical noteFunding Information:
We acknowledge the research support of LK as part of a summer fellowship program from Scripps College, Claremont, CA. We enthusiastically thank Dr. Christopher A. Lipinski, Senior Research Fellow, Pfizer Global Research and Development, who as an anonymous reviewer, provided most of the CAS numbers in the Tables, and thereby has facilitated the use of these results by the scientific community.
- Bile salts
- Drug absorption
- Octanol water partition coefficient