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Poonam Parashar,Naresh Diwaker,Jovita Kanoujia,Mahendra Singh,Abhishek Yadav,Indu Singh,Shubhini A. Saraf 한국약제학회 2020 Journal of Pharmaceutical Investigation Vol.50 No.1
Purpose Treatment of epilepsy faces immense challenge and often fails due to pharmaco-resistance and incapability of antiepileptic drug to cross the blood brain barrier (BBB). This problem demands an alternate, newer effective delivery approach. The intranasal drug delivery has emerged as a preferential route because of its ability to deliver drug directly to brain, facilitated through unique anatomy of the nasal cavity. The purpose of present study was to formulate and characterize in situ gel of lamotrigine (LGT) for delivery via nasal route. Methods The in situ gel was prepared using cold method utilizing sodium alginate, chitosan and methyl cellulose. The in vitro characterization of gel was performed for pH, gelation, drug content, viscosity, gel strength, in vitro release, and mucoadhesive strength. Results The clear in situ gel consisting of sodium alginate (0.05% w/v) and chitosan (0.25% w/v), showed 76.05% drug release in 8 h with pH 5.30 ± 0.07, drug content 94.93% and gel strength 46.00 ± 2.00 s. Further, the optimized (IG8) formulation was subjected for ex vivo permeation study and histopathological analysis. The amount of LGT in brain and plasma was determined pharmacokinetically in rat model. An enhanced brain concentration (200% approximately) of LGT was achieved (AUC last 9.33 ± 2.54 μg h/mL, Cmax 1.41 ± 0.15 μg/mL) in case of in situ gel when compared with oral drug suspension (AUC last 4.78 ± 1.98 mcg h/mL, Cmax 0.84 ± 0.28 μg/mL). Conclusion In situ gel of LGT via intranasal route can be taken as a viable alternative to the conventional antiepileptic drug delivery.