The lyotropic polymorphism of two pharmacologically active molecules

The two drugs considered are amiodarone hydrochloride (AC), used in heart therapy and palmitoyl timolol malonate (PTM), a prodrug of timolol and a medicament for glaucoma. These crystalline compounds are poorly soluble in water at room temperature, but form transparent phases, which are sols or gels, much more concentrated than the critical micellar concentration (CMC), when 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-solutions were also obtained by dissolution in chloroform, followed by rapid solvent evaporation and addition of water. A lamellar phase was also observed, with its classical textures: myelin forms, oily streaks and polygonal fields. Two transparent and isotropic phases, one more concentrated than the lamellar phase and the other one less concentrated, are presumed to be inverse sponges. The water-rich phase, mainly studied with amiodarone, formed a milky cloud on further dilution and a model has been proposed. From these two examples, some remarks of a geometrical kind are presented on the rich polymorphism of certain water-lipid systems.