Thermoreversible Carbamazepine In Situ Gel for Intranasal Delivery: Development and In Vitro, Ex Vivo Evaluation

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Intranasal (IN) drug delivery is emerging as a viable alternative for targeting the brain.
• Carbamazepine (CBZ) is conventionally administered orally.
• Developing effective IN formulations for direct brain delivery is crucial.

Purpose of the Study:

• To develop and optimize a thermoreversible in situ gelling system for intranasal delivery of carbamazepine (CBZ).
• To evaluate the physicochemical properties, in vitro release, and ex vivo permeation of the developed CBZ in situ gel.
• To assess the safety of the formulation for nasal mucosa.

Main Methods:

• A cold method was used to synthesize thermoreversible gels using poloxamer 407 (P407) and iota carrageenan (ɩ-Cg).
• Physicochemical properties (gelation temperature, pH, rheology, mucoadhesion) were characterized.
• In vitro drug release and ex vivo permeation studies through goat nasal mucosa were performed.
• Release kinetics were analyzed using the Korsmeyer-Peppas model.

Main Results:

• Optimized gels exhibited suitable gelation temperatures (28-33°C), pH (4.5-6.5), pseudoplastic rheological behavior, and significant mucoadhesive strength.
• The in situ gel demonstrated sustained carbamazepine release over 24 hours, fitting the non-Fickian diffusion model.
• Ex vivo studies showed sustained permeation with high drug penetration (243.94 µg/cm²) and flux (10.16 µg/cm²/h) without affecting nasal mucosa integrity.

Conclusions:

• The developed thermoreversible in situ gelling system is a promising platform for intranasal carbamazepine delivery.
• This formulation facilitates direct brain targeting by bypassing the blood-brain barrier.
• The nasal delivery approach proved safe and effective for enhanced drug permeation.