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KMID : 1146920210510020199
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Journal of Pharmaceutical Investigation
2021 Volume.51 No. 2 p.199 ~ p.211
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Thermosensitive nasal in situ gelling systems of rufinamide formulated using modified tamarind seed xyloglucan for direct nose-to-brain delivery: design, physical characterization, and in vivo evaluation
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Dalvi Avantika V.
Ravi Punna R.
Uppuluri Chandra T.
Mahajan Radhika R.
Katke Sumeet V.
Deshpande Vibha S.
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Abstract
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Purpose: Rufinamide is an anti-epileptic drug approved for use in children?≥?4 years of age and in adults. It is marketed as Banzel in the USA. In 2015, Banzel received approval for use in pediatric patients (1?4 years of age) and the patent for which expires in 2023. It suffers from poor oral bioavailability, and hence, small amounts of the drug reach the brain. This has led to high and frequent dosage administration of rufinamide. This work aims to improve its brain bioavailability by formulating a nasal thermosensitive in situ gel using xyloglucan.
Methods: The formulation was optimized using rheometric analysis, texture analysis, in vitro, and in vivo studies. Pharmacokinetic studies in rats were carried out to assess direct nose to brain uptake for the optimized in situ gelling formulation of rufinamide and compared with intravenous bolus and aqueous nasal suspension of rufinamide. Finally, brain targeting indices % DTE, and % DTP were calculated.
Results: All the formulations showed gelation below 35 °C. The final formulation comprised 2.0% w/v xyloglucan, 0.01% v/v thiomersal (preservative), and rufinamide in suspended form. The %DTE values for the in-situ gel formulation and aqueous suspension were 1069.94 and 146.88, and the %DTP values were 90.65 and 31.91, respectively.
Conclusion: This work demonstrated the superiority of the nasal gel formulation over oral formulation of rufinamide. If translated to humans, this would definitely help patients suffering from epilepsy, especially pediatric population, in whose case, a high dose and frequent dosage administration via oral route is inconvenient.
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KEYWORD
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Rufinamide, Nose to brain delivery, Pharmacokinetics, Thermoresponsive gel, Xyloglucan
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