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Novel Sprayable Thermosensitive Benzydamine Hydrogels for Topical Application: Development, Characterization, and In Vitro Biological Activities

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Abstract

Benzydamine hydrochloride (BZD) having analgesic, anesthetic, and anti-inflammatory effects is used orally or topically in the treatment of disorders such as joint inflammation and muscle pain. Within the scope of this study, sprayable thermosensitive BZD hydrogels were developed using thermoresponsive poloxamers to avoid systemic side effects and to provide better compliance for topical administration. Also, hydroxypropyl methyl cellulose (HPMC) was employed to improve the mechanical strength and bioadhesive properties of the hydrogel. The addition of BZD generally decreased the viscosity of the formulations (p < 0.05), while increasing the gelation temperature (p < 0.05). The formulations that did not have any clogs or leaks in the nozzle of the bottle during the spraying process were considered lead formulations. To spray the formulations easily, it was found that the viscosity at RT should be less than 200 mPa·s, and their gelation temperature should be between 26 and 34°C. Increasing HPMC and poloxamer improved bioadhesion. The amount of HPMC and poloxamers did not cause a significant change in the release characteristics of the formulations (p > 0.05); the release profiles of BZD from the formulations were similar according to model-independent kinetic (f2 > 50). HPMC and poloxamers had important roles in the accumulation of BZD in the skin. In vitro biological activity studies demonstrated that the formulations presented their anti-inflammatory activity with TNF-α inhibition but did not have any effect on the inhibition of COX enzymes as expected. As a result, thermosensitive hydrogels containing BZD might be an appropriate alternative, providing an advantage in terms of easier application compared to conventional gels.

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Data Availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank Humanis (Turkey) for donating benzydamine hydrochloride and BASF Chemicals (Germany) for donating P407, P188, and HPMC K4M.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, School of Pharmacy, Istanbul Medipol University, 34815, Istanbul, Turkey

    Muhammet Davut Arpa & Ebrar Elif Kesmen

  2. Department of Microbiology, School of Pharmacy, Istanbul Medipol University, 34815, Istanbul, Turkey

    Sevde Nur Biltekin

  3. Department of Molecular Biology and Genetics, Institute of Graduated Studies in Science, Istanbul University, 34116, Istanbul, Turkey

    Sevde Nur Biltekin

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  3. Sevde Nur Biltekin
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Contributions

MDA: supervision, project administration, investigation, methodology, funding acquisition, writing—original draft, and writing—review and editing; EEK: investigation and methodology; SNB: investigation, methodology, funding acquisition, and writing—original draft

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Correspondence to Muhammet Davut Arpa.

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Arpa, M.D., Kesmen, E.E. & Biltekin, S.N. Novel Sprayable Thermosensitive Benzydamine Hydrogels for Topical Application: Development, Characterization, and In Vitro Biological Activities. AAPS PharmSciTech 24, 214 (2023). https://doi.org/10.1208/s12249-023-02674-w

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