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Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment

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Abstract

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

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Data Availability

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

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Acknowledgements

The authors thank the Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, and the School of Engineering and Technology, Walailak University, for support and facilitation. We also thank the Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, for help and motivation.

Funding

This research was supported with the grant No. SURDI: Postdoctoral/66/5 by Silpakorn University under the postdoctoral fellowship program.

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Authors and Affiliations

  1. Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand

    Ei Mon Khaing & Thawatchai Phaechamud

  2. Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand

    Setthapong Senarat

  3. Natural Bioactive and Material for Health Promotion and Drug Delivery System Group (NBM), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand

    Setthapong Senarat, Kritamorn Jitrangsri & Thawatchai Phaechamud

  4. Department of Chemical Engineering and Pharmaceutical Chemistry, School of Engineering and Technology, Walailak University, Nakhon Srithammarat, 80160, Thailand

    Kritamorn Jitrangsri

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Contributions

Conceptualization: T.P.; methodology: E.M.K. and S.S.; validation: K.J. and S.S.; investigation: E.M.K., S.S., and T.P.; writing—original draft preparation: E.M.K., S.S., and T.P.; writing—review and editing: K.J. and T.P.; supervision: K. J. and T.P.; project administration: T.P.; funding acquisition: T.P. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Thawatchai Phaechamud.

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Highlights

• Fluconazole in situ gel oral spray was fabricated using ibuprofen as a gelling agent.

• Higher ibuprofen loading reduced surface tension and retarded solvent exchange.

• The developed system effectively inhibited various Candida species and showed in vitro anti-inflammatory activity.

• Cremophor EL addition increased fluconazole and ibuprofen tissue permeations.

• Fluconazole-loaded ibuprofen in situ gel-based oral spray presents as a promising dosage form for oropharyngeal candidiasis treatment.

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Khaing, E.M., Senarat, S., Jitrangsri, K. et al. Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment. AAPS PharmSciTech 25, 89 (2024). https://doi.org/10.1208/s12249-024-02804-y

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