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Objective <p>This study aimed to develop and optimize a thermosensitive in-situ nasal gel of teriflunomide for effective CNS targeting in the treatment of multiple sclerosis.</p> Methods <p>A 2³ factorial design was employed to investigate the effects of Poloxamer 407 concentration, HPMC K4M concentration, and stirring speed on gelation temperature, viscosity, mucoadhesive strength, and drug release. The optimized gel was evaluated for clarity, pH, drug content, spreadability, and in vitro drug release.</p> Results <p>The optimized formulation exhibited a pH of 6.12 ± 0.04, a gelation temperature of 32.1 ± 0.3&#xa0;°C, a viscosity of 3925 ± 112 cps, and a mucoadhesive strength of 1385 ± 27 dynes/cm². Drug content was 99.28 ± 1.14%, and in vitro release showed 98.52% drug release over 24&#xa0;h, following Higuchi diffusion-controlled kinetics.</p> Conclusion <p>The developed nasal in-situ gel demonstrated suitable physicochemical characteristics, sustained drug release, and enhanced nasal residence, indicating strong potential for nose-to-brain delivery of teriflunomide in multiple sclerosis therapy.</p> Graphical Abstract <p></p>

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Development of a Thermosensitive In-Situ Nasal Gel of Teriflunomide for Targeted CNS Delivery in Multiple Sclerosis

  • 期刊论文

  • 发表日期：

    2025年11月27日

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  • Kiran Dudhat,
  • Yash Kachhadiya,
  • Malaykumar Chotaliya

摘要

Objective

This study aimed to develop and optimize a thermosensitive in-situ nasal gel of teriflunomide for effective CNS targeting in the treatment of multiple sclerosis.

Methods

A 2³ factorial design was employed to investigate the effects of Poloxamer 407 concentration, HPMC K4M concentration, and stirring speed on gelation temperature, viscosity, mucoadhesive strength, and drug release. The optimized gel was evaluated for clarity, pH, drug content, spreadability, and in vitro drug release.

Results

The optimized formulation exhibited a pH of 6.12 ± 0.04, a gelation temperature of 32.1 ± 0.3 °C, a viscosity of 3925 ± 112 cps, and a mucoadhesive strength of 1385 ± 27 dynes/cm². Drug content was 99.28 ± 1.14%, and in vitro release showed 98.52% drug release over 24 h, following Higuchi diffusion-controlled kinetics.

Conclusion

The developed nasal in-situ gel demonstrated suitable physicochemical characteristics, sustained drug release, and enhanced nasal residence, indicating strong potential for nose-to-brain delivery of teriflunomide in multiple sclerosis therapy.

Graphical Abstract