The influence of water on phase transitions of a drug-loaded reverse micellar solution into lamellar liquid crystals

The effects of timolol maleate (TM) as a model drug on the physicochemical properties of a reverse micellar solution (RMS) consisting of lecithin in isopropyl myristate were investigated in this study. Special attention was focused on one-dimensional growing of micelles to giant worm-like associates on addition of water and on a subsequent phase transition to lamellar liquid crystals. Reverse micellar solutions with different water and drug contents were examined with photon correlation spectroscopy (PCS), P-31-NMR and oscillation theology. Lamellar mesophases arise at higher water contents, characterized with polarization microscopy and small-angle X-ray diffraction (SAXD). It was concluded that timolol maleate interacts with the phosphate group of lecithin. These interactions between TM and lecithin are proposed to cause a branching as well as a truncation of the micellar associates. Since the unloaded micelles were found to be larger than those containing TM at the same water content, the interaction between TM and lecithin obviously hinders the formation of associates such as worm-like micelles or planar lamellae to some extent. Furthermore, the viscosity of the RMS is reduced even at small drug loads,which indicates that TM prevents the formation of a network of entangled worm-like micelles. Finally, the entanglement of the unloaded worm-like micelles was identified as a high viscous sol, which transforms into a low viscous gel on further addition of water. As a hypothesis, this gel state was assumed to be a sponge-like phase. (C) 2001 Elsevier Science B.V. All rights reserved.