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

The zwitterionic detergent hexadecylphosphocholine (HDPC) is structurally s imilar to the phospholipids present in natural membranes, and the study of the drug/HDPC micelle interaction can be of interest in drug-activity relat ionship studies. The effect of these micelles on the spectroscopic, acid-ba se and solubility properties of two non-steroidal anti-inflammatory drugs, indomethacin and acemetacin, was studied at different pH values. From the d ependence of these physical properties on HDPC concentration, by fitting ma thematical models based on the simple partition of the drugs between two ps eudo-phases to the data, it was possible to calculate the drug/micelle bind ing constants, which can be related to the water/micelle partition coeffici ents. 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 c alculate the binding constants for the neutral and negative forms of the dr ugs (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 p H conditions that can be troublesome, related with drug stability or solubi lity problems. (C) 2001 Elsevier Science B.V. All rights reserved.