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In situ gel of lamotrigine for augmented brain delivery: development characterization and pharmacokinetic evaluation

  • Poonam Parashar
  • Naresh Diwaker
  • Jovita Kanoujia
  • Mahendra Singh
  • Abhishek Yadav
  • Indu Singh
  • Shubhini A. SarafEmail author
Original Article
  • 6 Downloads

Abstract

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.

Keywords

Nasal gel Brain delivery Pharmacokinetics Intranasal administration 

Notes

Acknowledgements

Authors are grateful to UGC for providing financial support.

Compliance with ethical standards

Ethical Approval

Authors have complied with ethical standards required for animal experimentation.

Conflict of interest

The authors have no conflicts of interest to declare.

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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  • Poonam Parashar
    • 1
  • Naresh Diwaker
    • 1
  • Jovita Kanoujia
    • 1
  • Mahendra Singh
    • 1
  • Abhishek Yadav
    • 1
  • Indu Singh
    • 1
    • 2
  • Shubhini A. Saraf
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences, School of Biosciences & BiotechnologyBabasaheb Bhimrao Ambedkar University (A Central University)LucknowIndia
  2. 2.Amity Institute of PharmacyAmity UniversityNoidaIndia

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