Design and Characterization of Doxepin In-situ Nasal Gel Using Pectin as a Bio-compatible Matrix

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Neuropharmacology

Background:

• Trans-nasal drug delivery offers a direct route to the brain, bypassing the blood-brain barrier.
• Doxepin hydrochloride is an antidepressant with potential for improved delivery via novel formulations.
• Ion-triggered gels present a promising approach for controlled and targeted drug release.

Purpose of the Study:

• To formulate and characterize an ion-triggered trans-nasal gel of Doxepin hydrochloride.
• To evaluate the physicochemical properties and in vitro/ex vivo performance of the developed gels.
• To assess the in vivo efficacy of the optimized formulation in a preclinical model of depression.

Main Methods:

• Formulation of Doxepin hydrochloride gels using pectin and hydroxypropyl methylcellulose (HPMC) K4M.
• Evaluation of gel properties: gel strength, gelation time, viscosity, mucoadhesion, drug content, and stability.
• Ex vivo drug permeation studies using sheep nasal mucosa.
• Assessment of locomotor activity and mobility in mice treated with the optimized formulation.

Main Results:

• Increased concentrations of pectin and HPMC K4M enhanced mucoadhesive strength and viscosity.
• The optimized formulation (C2F2, 3.5% pectin, 1.5% HPMC) achieved 97.96% drug release via sheep nasal mucosa.
• The formulation demonstrated good stability over three months, with no significant changes in viscosity, pH, or drug content.
• In vivo studies indicated enhanced locomotor activity and mobility in mice.

Conclusions:

• Ion-triggered trans-nasal Doxepin hydrochloride gels can be successfully formulated.
• The optimized formulation exhibits favorable physicochemical properties and enhanced ex vivo drug release.
• The developed nasal gel formulation shows potential for treating depression by improving locomotor activity.