Characterization and Antifungal Activity Evaluation of Clove Oil-Based Microemulsions Containing Fluconazole

Main Article Content

Prapaporn Boonme
Pinyapat Theerapisut
Pichamon Patcharawiroon
Sutasinee Ardhanwanich
Thawatchai Phaechamud

Abstract

Topical drug delivery represents an effective approach for the management of cutaneous fungal infections, as it minimizes the risk of systemic adverse effects. Nevertheless, successful formulation design requires adequate enhancement of drug permeation through the skin barrier. The present study aimed to develop clove oil-based microemulsions incorporating 2% w/w fluconazole. Four formulations were selected from the microemulsion region identified through the construction of a pseudoternary phase diagram comprising clove oil, 1:1 mixture of water and propylene glycol, and Tween 80. The properties of the formulations, along with their antifungal activity against four Candida species including C. albicans, C. krusei, C. lusitaniae and C. tropicalis were evaluated. The experimental results indicated that all prepared formulations were oil-in-water microemulsions. They appeared as clear yellow liquids. Their pH and viscosity values were within an acceptable range for topical application. All clove oil-based microemulsions demonstrated antifungal activity against the tested strains, which can be attributed to eugenol, the principal constituent of clove oil. The inhibition zone diameter ranged from 23.0-30.3 millimeters for fluconazole-loaded microemulsions, which was significantly greater than that of the corresponding blank formulations. This research revealed that the developed clove oil-based microemulsions containing fluconazole show promise as topical antifungal formulations and warrant further investigation. The most interesting formulation for further study was FLZ-ME-1 which was composed of fluconazole, clove oil, 1:1 mixture of water and propylene glycol, and Tween 80 at 2.0%, 9.8%, 49% and 39.2% w/w, respectively.

Article Details

Section
Science and Health Science & Sport

References

Badr-Eldin, S. M., Aldawsari, H. M., Kotta, S., & Elfaky, M. A. (2024). Augmentation of antifungal activity of fluconazole using a clove oil nanoemulgel formulation optimized by factorial randomized D-optimal design. 3 Biotech, 14(11), 270. https://doi.org/10.1007/s13205-024-04116-1

Febriyenti, F., Suharti, N., & Putri, R. F. (2022). Formulation and evaluation of patchouli oil microemulsion and microemulgel for inhibit the bacterial growth. Research Journal of Pharmacy and Technology, 15(1), 51-55. https://doi.org/10.52711/0974-360X.2022.00010

Havlickova, B., Czaika, V. A., & Friedrich, M. (2008). Epidemiological trends in skin mycoses worldwide. Mycoses, 51(Suppl.4), 2-15. https://doi.org/10.1111/j.1439-0507.2008.01606.x

Hay, R. (2018). Therapy of skin, hair and nail fungal infections. Journal of Fungi, 4(3), 99. https://doi.org/10.3390/jof4030099

Jitrangsri, K., Puyathorn, N., Rein, S. M. T., Sirirak, J., Chomto, P., & Phaechamud, T. (2026). Solvent removal salicylic acid-loaded myristic acid-based in situ forming gel. Gels, 12(3), 220. https://doi.org/10.3390/gels12030220

Kiromah, N. Z. W., Sugihartini, N., & Nurani, L. H. (2023). Development and characterization of clove oil microemulsion. Pharmacia, 70(1), 233-241. https://doi.org/10.3897/pharmacia.70.e98096

Kruithoff, C., Gamal, A., McCormick, T. S., & Ghannoum, M. A. (2024). Dermatophyte infections worldwide: increase in incidence and associated antifungal resistance. Life, 14(1), 1. https://doi.org/10.3390/life14010001

Lopes, L. B. (2014). Overcoming the cutaneous barrier with microemulsions. Pharmaceutics, 6(1), 52-77. https://doi.org/10.3390/pharmaceutics6010052

Marchese, A., Barbieri, R., Coppo, E., Orhan, I. E., Daglia, M., Nabavi, S. F., Izadi, M., Abdollahi, M., Nabavi, S. M., & Ajami, M. (2017). Antimicrobial activity of eugenol and essential oils containing eugenol: a mechanistic viewpoint. Critical Reviews in Microbiology, 43(6), 668-689. https://doi.org/10.1080/1040841X.2017.1295225

Pal, R. (1996). Effect of droplet size on the rheology of emulsions. AIChE Journal, 42(11), 3181-3190. https://doi.org/10.1002/aic.690421119

Promjan, S., & Boonme, P. (2023). Itraconazole-loaded microemulsions: formulation, characterization, and dermal delivery using shed snakeskin as the model membrane. Pharmaceutical Development and Technology, 28(1), 51-60. https://doi.org/10.1080/10837450.2022.2162082

Puyathorn, N., Senarat, S., Lertsuphotvanit, N., & Phaechamud, T. (2023). Physicochemical and bioactivity characteristics of doxycycline hyclate-loaded solvent removal-induced ibuprofen-based in situ forming gel. Gels, 9(2), 128. https://doi.org/10.3390/gels9020128

Salomon, G., & Giordano-Labadie, F. (2022). Surfactant irritations and allergies. European Journal of Dermatology, 32(6), 677-681. https://doi.org/10.1684/ejd.2022.4290

Shendge, P., Desai, A., & Kesare, S. S. (2022). The use of fluconazole in the treatment of superficial fungal infections - a meta-analysis. IP Indian Journal of Clinical and Experimental Dermatology, 8(2), 101-106. https://doi.org/10.18231/j.ijced.2022.023

Souto, E. B., Doktorovova, S., & Boonme, P. (2011). Lipid-based colloidal systems (nanoparticles, microemulsions) for drug delivery to the skin: materials and end-product formulations. Journal of Drug Delivery Science and Technology, 21(1), 43-54. https://doi.org/10.1016/S1773-2247(11)50005-X

Wuttikul, K., & Boonme, P. (2016). Formation of microemulsions for using as cosmeceutical delivery systems: effects of various components and characteristics of some formulations. Drug Delivery and Translational Research, 6(3), 254-262. https://doi.org/10.1007/s13346-016-0279-x