Biopharmaceutical profile of a clotrimazole nanoemulsion: Evaluation on skin and mucosae as anticandidal agent

Abstract Clotrimazole (CLT) was formulated in a nanoemulsion (NE) for the topical treatment of candidiasis consisting of 10% labrafac ® lipophile, 60% labrasol ® :capryol ® 90 mixture (ratio 4:1) and 30% propylene glycol. Physicochemical properties, stability, rheology , in vitro drug release, ex vivo drug permeation through human skin and porcine buccal, sublingual and vaginal mucosae, antifungal efficacy, as well as in vivo skin tolerance were evaluated. 1% CLT-NE (CLT-NE1) and 2% CLT-NE (CLT-NE2) exhibited 153 ± 17.25 and 186 ± 15.38 nm droplet sizes, low polydispersity indexes, negative zeta potentials and biocompatible pH values. The CLT-NEs exhibited typical Newtonian profiles with viscosities of 42.14 ± 0.037 mPa·s and 41.35 ± 0.041 mPa·s, respectively and higher extensibility properties than commercial counterparts retaining their physicochemical properties for 180 days. NEs provided a sustained release of drug according to the first order model. Similar skin permeation properties were observed between CLT-NE1 and commercial reference. However, significant higher CLT amounts retained in mucosae were provided by CLT-NE2 when compared with references. Antifungal efficacies were also higher than commercial references, and the in vivo tolerance study confirmed the suitability for topical application, making CLT-NEs a great tool for clinical investigation of topical candidiasis treatments.