Drug Solubilization and Interaction in Bile Salt Systems

Abstract

The bile salts, which are naturally occurring steroidal surfactants, aid in the digestion, emulsification, and absorption of dietary lipids and the transport of drugs across the intestinal wall. Drug-bile salt interactions in aqueous and nonaqueous solvent systems have been investigated using nmr spectroscopic techniques. The compounds selected for this investigation were chosen because of their structural diversity and are representative of a wide variety of drug types. Nmr provides a nondestructive, nonperturbing and sensitive method of probing the microenvironment, structure, and binding sites of interactive molecular assemblies as well as their reactivity with additives. The effects of varying the concentration of the bile salt and of the drug upon the ¹H and ¹³C chemical shifts have been determined. The nuclei which show the greatest changes with increasing concentration are those which interact to the greatest extent and consequently are those which are located at or near the binding site(s) of the solubilized drug. Both the interactions and the reactivity of the drugs are explicable in terms of their structural geometry and that of the associated, or "micellar," bile salt.