Interaction of drugs with hexadecylphosphocholine micelles. Derivative spectroscopy, acid-base and solubility studies

The zwitterionic detergent hexadecylphosphocholine (HDPC) is structurally similar to the phospholipids present in natural membranes, and the study of the drug/HDPC micelle interaction can be of interest in drug-activity relationship studies. The effect of these micelles on the spectroscopic, acid-base and solubility properties of two non-steroidal anti-inflammatory drugs, indomethacin and acemetacin, was studied at different pH values. From the dependence of these physical properties on HDPC concentration, by fitting mathematical models based on the simple partition of the drugs between two pseudo-phases to the data, it was possible to calculate the drug/micelle binding constants, which can be related to the water/micelle partition coefficients. It was found that the three techniques yield similar results and that by performing the determinations at any two pH values, it is possible to calculate the binding constants for the neutral and negative forms of the drugs (K-b(AH) and K-b(A-)). Furthermore, the knowledge of K-b(AH) and K-b(A-) allows the prediction of K-b(T) for any given pH, avoiding experimental pH conditions that can be troublesome, related with drug stability or solubility problems. (C) 2001 Elsevier Science B.V. All rights reserved.