Multivariate Optimization of Carbamazepine-Loaded Nanostructured Lipid Carriers for Brain Targeting and Epilepsy Management

The growth of nanostructured lipid carriers for brain targeting shows a promising strategy for escalating the therapeutic efficacy of antiepileptic drugs such as carbamazepine (CBZ). CBZ is a drug of choice in the management of epilepsy and trigeminal neuralgia. However, CBZ oral administration is associated with poor bioavailability, successive dose adjustments, and long-term adverse effects. The current research was intended to develop brain-targeted CBZ-loaded nanostructured lipid carriers (CBZ-NLCs) with the help of the design of experiments to improve anti-epileptic potential. The CBZ-NLCs were fabricated by using an ultrasonication approach using different surfactants such as Tween 80, Compritol ATO 888, and oleic acid. The different formulation variables were screened with the help of the Plackett–Burman design which significantly affects the development of CBZ-NLCs. The Box-Behnken design is employed to assess the interactions between these formulation parameters and the variability between the different batches. In the Plackett–Burman design, Pareto ranking analyses indicated that the amount of solid lipid, concentration of surfactant, speed of homogenization, and homogenization time significantly affected the formulation of CBZ-NLCs. These variables were further evaluated employing the Box-Behnken design. The outcome of the Box-Behnken design was authenticated by preparing the recommended optimized solution, which yielded 205 ± 0.87 nm particle size along with an adequately superior entrapment efficiency of 75.21 ± 0.98% and 74.89 ± 1.01% cumulative drug release in 24 h. The plasma concentration, along with the absorption rate, was greater compared to that of the CBZ solution. AUC for the fabricated formulation was 985.32 ± 21.25 µg h/ml while 245 ± 1.11 µg h/ml for CBZ. The groups treated with CBZ-NLCs and diazepam had a 100% survival rate, and the groups treated with saline and CBZ dispersion had 100% and 30% fatality rates, respectively. It could be concluded that the application of experimental design is a helpful tool for the development of CBZ-NLCs. The prepared formulation could be administered via the non-invasive nasal route and shall be effective in the management of epilepsy.