Formulation Development and Evaluation of Thermo-Responsive BIOGELS: Nose to Brain Approach

Abstract

With an increase in nasal residence time, thermoreversible biogels can be useful as drug delivery methods. The purpose of this research was to develop a thermoreversible method for intranasal administration of doxepin using chitosan and glycerophosphate. To create the formulations, chitosan, glycerophosphate, polyethylene glycol, and the antidepressant doxepin hydrochloride were mixed in the appropriate concentrations. The gelling properties, rheology, mucoadhesion, in vitro release, and ex vivo penetration through sheep nasal mucosa of both systems were tested. Swiss albino mice were used for the forced swim test to determine the effectiveness in vivo. Mice that were repeatedly exposed to the formulation had nasal tissues examined histologically to see how the exposure affected them. All three formulations displayed thixotropy and gelled quickly at 37 degrees Celsius, then reverted to a sol upon cooling. Polyethylene glycol was added to make the formula isotonic and reduce the amount of glycerophosphate needed for gelation. The measured pharmacodynamic parameter suggested the formulation was effective in treated groups, and histopathological reports from those groups showed no substantial local toxicity. The biogels show promise as a platform for developing nasal medication delivery devices.