The lyotropic polymorphism of two pharmacologically active molecules

The two drugs considered are amiodarone hydrochloride (AC), used in heart t herapy and palmitoyl timolol malonate (PTM), a prodrug of timolol and a med icament for glaucoma. These crystalline compounds are poorly soluble in wat er at room temperature, but form transparent phases, which are sols or gels , much more concentrated than the critical micellar concentration (CMC), wh en the crystals are heated in the presence of water to temperatures from 50 to 80 degrees C and cooled to room temperature. These transparent pseudo-s olutions were also obtained by dissolution in chloroform, followed by rapid solvent evaporation and addition of water. A lamellar phase was also obser ved, with its classical textures: myelin forms, oily streaks and polygonal fields. Two transparent and isotropic phases, one more concentrated than th e lamellar phase and the other one less concentrated, are presumed to be in verse sponges. The water-rich phase, mainly studied with amiodarone, formed a milky cloud on further dilution and a model has been proposed. From thes e two examples, some remarks of a geometrical kind are presented on the ric h polymorphism of certain water-lipid systems.