Abstract
Background: Vulvovaginal candidiasis (VVC) is one of the most common fungal infections affecting women, typically caused by Candida albicans. Conventional clotrimazole (CLT) formulations provide limited relief because of their short residence time and poor drug dissolution at the vaginal site. In this study, Bulgarian rose oil (BRO) was selected as a functional, bioactive oil phase to develop a microemulsion (ME) incorporated into a thermosensitive, mucoadhesive in situ gel. The system was designed to simultaneously overcome CLT solubility issues and improve local antifungal retention. Methods: The ME was prepared using BRO, Tween 60, and Transcutol P and optimized for droplet size, stability, and release performance. Results: The selected formulation (ME3) consisted of uniform nanosized droplets (~27 nm). It exhibited a clear appearance and a faster drug release rate (76% in 6 h) than the CLT suspension. Incorporating ME3 into a thermosensitive gel containing Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose (HPMC) K4M produced a transparent microgel (MG) system that gelled near body temperature (35.4 °C) and exhibited suitable viscosity and pH. The MG produced a larger inhibition zone (43 mm) against Candida albicans than both the plain gel and a marketed product (32–33 mm). No signs of irritation were observed in rabbits, and microscopy confirmed the uniform distribution of ME droplets within the gel matrix. Conclusion: Overall, this MG formulation combined effective antifungal activity with good tissue compatibility and prolonged drug release, suggesting its potential as a more convenient and sustained local therapy.