Phase behavior, rheology, and release from liquid crystalline phases containing combinations of glycerol monooleate, glyceryl monooleyl ether, propylene glycol, and water

Abstract

Liquid crystalline phases can be used as slow-release matrices, where the release can be enhanced or suppressed via triggered phase transitions. Detailed knowledge of relevant phase diagrams is necessary, however, to control phase transitions under specific triggers. Here we complete the phase diagram of a quaternary system composed of glycerol monooleate (GMO), glyceryl monooleyl ether (GME), propylene glycol (PG), and water (W). All samples are studied at two temperatures (room and skin temperature). The liquid crystalline phases are characterized using visual inspection, small-angle X-ray diffraction (SAXD), and rheology. Cubic, reversed hexagonal, lamellar, and sponge phases are observed depending on the sample composition. The cubic and reversed hexagonal phases show typical rheological properties associated with the respective phase, i.e., a stiff gel for the cubic phase with little frequency dependence, and a weaker gel whose absolute values vary with frequency in the case of the reversed hexagonal phase. Furthermore, a triggered phase transition from cubic to reversed hexagonal is observed in specific formulations upon alteration of water and PG content and temperature variation. Release of a model drug from selected compositions shows a slow release rate, where the reversed hexagonal phase reduces the release rate more than the cubic phase does. The study reveals for the first time the complete phase diagram of the quaternary system of GMO/GME/PG/W, which can be used for slow drug delivery via the change from the cubic phase to the reversed hexagonal phase.