Improved solubilization of carbamazepine and structural transitions in nonionic microemulsions upon aqueous phase dilution

Abstract

Solubilization capacity and structural transformations in nonionic microemulsions characterized by a large continuous isotropic region forming dilutable self-assembled nanodroplets containing solubilized carbamazepine, were studied along dilution lines 73 and 82 (70 and 80 wt% surfactant and 30 and 20 wt% of oil phase, respectively). The preparations were based on pharma-grade ingredients, water, R-(+)-limonene, ethanol, propylene glycol, and Tween 60. Solubilization capacity (SC) of the drug was dependent on the microstructure of the microemulsion and on the surfactant-to-oil phase weight ratio. The SC in the concentrate (reversed micelles) was 15 times higher than its solubility in the oil. Transition of the W/O microemulsion to a bicontinuous phase and to O/W droplets were indentified by electrical conductivity, viscosity, SAXS, and SD-NMR measurements. Once the system is diluted to 90 wt% aqueous phase, the SC is 10 and 16-fold higher, along dilution lines 73 and 82, respectively, than in pure water. Being solubilized, carbamazepine serves as a cosurfactant therefore it affects the curvatures of the microstructures and consequently the boundaries of the structural regions and the transition points between the different phases. Dilutable microemulsions are promising new carbamazepine vehicles for oral intake.