Exploring the Phase Behavior of Monoolein/Oleic Acid/Water Systems for Enhanced Donezepil Administration for Alzheimer Disease Treatment

Abstract

Donepezil is a drug usually administered by oral route for Alzheimer disease treatment, but several gastric side effects have been reported as diarrhea, nausea, and anorexia. We explored the phase behavior of lyotropic liquid crystalline (LLC) mesophases composed by monoolein/oleic acid/water for enhanced administration of donepezil. Polarized light microscopy suggested that these systems ranged from isotropic inverse micellar solutions (L2) to viscous and birefringent reverse hexagonal (HII) mesophases according to the amount of water in the ternary systems. Phase transition was observed from a L2 phase to HII mesophase after swelling studies, an interesting property to be explored as a precursor of LLC mesophases for mucosal administration that increases its viscosity in situ. Mucoadhesive properties of LLC mesophases were characterized using a texture analyzer indicating that these systems can have an increased residence time in the site of absorption. Donepezil-free base was incorporated in the evaluated formulations, and their in vitro release was controlled up to 24 h. The phase behavior of the systems demonstrated a great potential for enhanced donepezil administration once these mucoadhesive–controlled release formulations can incorporate the drug and prolong its release, possibly reducing its side effects.