Development of Carbamazepine Nanostructured Lipid Carrier Loaded Thermosensitive Gel for Intranasal Delivery

Abstract

Purpose: The present research work was designed to formulate and evaluate carbamazepine (CBZ) loaded nanostructured lipid carrier (NLC) based in-situ gel for nasal delivery. Methods: The NLC formulation of CBZ was prepared by microemulsion technique followed by probe sonication and evaluated for particle size, zeta potential, entrapment efficiency and in vitro drug diffusion. NLC formulation was incorporated into in-situ gelling formulation using poloxamer 407 (P407), poloxamer 188 (P188) and mucoadhesive polymer. The effect of concentration of poloxamer 188 (X1 ), type of mucoadhesive polymer (X2 ) and concentration of mucoadhesive polymer (X3 ) on gelling temperature (Y1 ) and drug diffusion after 8 h (Y2 ) was studied using Box-Behnken design. In vivo anticonvulsant activity of optimized formulation was studied in Wistar rats by maximal electro-convulsion model (MES). Results: The optimized CBZ NLC formulation, with 20% drug loading, 0.5:1 as Precirol:Capmul MCM ratio as lipid phase and 1:3 as Lipid:Smix ratio, resulted in 89.73±0.2% drug entrapment, 55.95±1.09% of drug diffusion after 8 h, particle size of 132.8 nm with polydispersity index of 0.302 and zeta potential of -29.2±6.1 mV. The in-situ gel formulation with 20% P407, 5% P188 and 0.2% chitosan was optimized and demonstrated excellent gelling ability, gelling temperature in the range of 30 to 35°C, 42.46% of drug diffusion in 8 h by Fickian diffusion mechanism and 31.34±0.76% of drug permeation through sheep nasal mucosa. In vitro anticonvulsant activity in MES model in rat demonstrated significant efficacy (71.95% protection against seizure in extension phase) as compared to plain in-situ nasal gel (50.26% protection against seizure in extension phase). Conclusion: NLC based in-situ gelling formulation demonstrated its potential for nasal delivery of CBZ with improved anticonvulsant activity.

Keywords

• carbamazepine
• nanostructured lipid carrier
• in-situ gel
• nasal permeation
• flux
• box-behnken design