Condensation of fluconazole and zinc undecylanate particles using low-pressure RF plasma: a novel drug combination approach.

BACKGROUND: Fluconazole (FCZ), a triazole antifungal agent, is routinely used in the treatment of various Candida infections, including oropharyngeal, esophageal, vulvovaginal candidiasis, candidemia, and disseminated candidiasis. Despite its broad safety profile, superior efficacy, and favorable pharmacokinetics, resistance to FCZ is an increasing clinical challenge. Zinc undecylenate (ZU), derived from castor oil, is an established topical antifungal agent with additional dermatological protective and immunoendocrinological properties. Combining these two pharmacotherapeutic agents presents a promising approach to overcoming fungal resistance, preventing biofilm formation, and reducing recurrence rates. METHODS: In this study, powdered ZU was condensed with powdered FCZ using low-pressure radiofrequency plasma (LPRFP). This plasma-assisted approach enabled the creation of a compound with sequential antifungal mechanisms. The condensed FCZ-ZU product was characterized and validated using nuclear magnetic resonance (NMR), optical emission spectrometry (OES), scanning electron microscopy (SEM), zeta potential, and particle size analyses. Statistical significance was determined using zeta potential and particle size data, with results evaluated at a threshold of p < 0.0001. RESULTS: The plasma-condensed FCZ-ZU compound demonstrated distinct physicochemical properties compared to the parent FCZ and ZU powders. Characterization confirmed the structural modification and condensation process, while particle size and zeta potential analyses indicated significant differences, supporting the creation of a novel compound (p < 0.0001). The sequential mechanism of action between FCZ and ZU suggested enhanced antifungal efficacy, reduced likelihood of resistance development, and inhibition of biofilm formation. CONCLUSIONS: This study successfully demonstrated, for the first time, the plasma-assisted condensation of FCZ with ZU into a single antifungal preparation. The novel compound has the potential to shorten treatment duration, prevent relapse, and overcome resistance in persistent and recurrent mycosis infections. The findings highlight LPRFP as a promising method for combining multiple pharmacotherapeutic agents into innovative formulations with enhanced clinical potential.