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KMID : 1146920200500010095
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Journal of Pharmaceutical Investigation
2020 Volume.50 No. 1 p.95 ~ p.105
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In situ gel of lamotrigine for augmented brain delivery: development characterization and pharmacokinetic evaluation
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Parashar Poonam
Diwaker Naresh
Kanoujia Jovita
Singh Mahendra
Yadav Abhishek
Singh Indu
Saraf Shubhini A.
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Abstract
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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 (AUClast 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 (AUClast 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.
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KEYWORD
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Nasal gel, Brain delivery, Pharmacokinetics, Intranasal administration
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