Design, in vitro, and in vivo evaluation of a new nanoemulsion gel of lamotrigine for application via nasal route

Aims: This study aimed to enhance the bioavailability and therapeutic efficacy of lamotrigine (LMG), an antiepileptic drug with low solubility, by formulating it into a nasal nanoemulsion (NE) for effective epilepsy control. Methods: LMG was incorporated into a nasal nanoemulsion (LMG-NE) using a 32 factorial design via spontaneous emulsification method. LMG-NEs were characterised for drug loading (DL), entrapment efficiency (EE%), particle size, microscopic examination, rheological profile, phosphatidylcholine liposome uptake, in vitro release, anticonvulsant activity, and in vivo pharmacokinetics. Results: The optimal formulation exhibited a DL of 79.03 ± 0.5 (w/w), an EE% of 80.2 ± 3.0%, a mean diameter of 182.78 ± 22.76 nm, and a zeta potential of 0.60 ± 0.04 mV. LMG was rapidly released, with 91.87% ± 4.54% of drug was released within 2 hours. The area under the curve (AUC0-24) showed a 1.84-fold increase compared to standard formulations. Conclusion: LMG-NE presents a promising alternative for epilepsy treatment, potentially reducing peripheral side effects and improving therapeutic outcomes.