Novel Pemulen/Pullulan blended hydrogel containing clotrimazole-loaded cationic nanocapsules: Evaluation of mucoadhesion and vaginal permeation.

In this work, hydrogels containing clotrimazole-loaded nanocapsules were developed through the innovative association of two mucoadhesive polymers: Pemulen® TR1 and Pullulan. Furthermore, the hydrogels macroscopic characteristics, pH and spreadability were evaluated. The formulations showed homogeneous appearance and pH compatible with vaginal application (around 5.0). Similar spreadability profiles were found in hydrogels containing clotrimazole-loaded nanocapsules and in the free drug as well. Hydrogels were evaluated considering their mucoadhesive potential by the falling liquid film method and the permeation/penetration capacity through cow vaginal mucosa in Franz cell. The results showed that the concentration of 3% Pullulan was important to increase the adhesive strength on the layer used (mucin gel or animal mucosa). The results of the permeation/penetration study showed that the hydrogel containing clotrimazole-loaded nanocapsules remained on the vaginal mucosa surface, what is ideal for the treatment of superficial vaginal infections. This way, the Pemulen/Pullulan blended hydrogel is a promising alternative for the treatment of vulvovaginal candidiasis.

Formulation and in vitro evaluation of coconut oil-core cationic nanocapsules intended for vaginal delivery of clotrimazole.

The objective of this work was to propose coconut oil-core nanocapsules prepared from Eudragit(®) RS100, a cationic polymer, and to evaluate their potential for vaginal delivery of clotrimazole in candidiasis. Nanocapsule suspensions loaded with clotrimazole at 1.0 and 3.0mg/mL were prepared by interfacial deposition of Eudragit(®) RS100. The physicochemical characterization showed average diameter lower than 200 nm, low polydispersity index, positive zeta potential (+10.94 to +14.57 mV), acid pH values (5.4-5.7) and encapsulation efficiencies close to 100%. After 60 days of storage at room temperature and protected from light, the nanocapsules were reasonably stable. Photodegradation studies showed that nanoencapsulation improved clotrimazole stability against UV radiation. The in vitro drug release at pH 4.5 was characterized by a prolonged release with no burst effect. The nanocapsules were more active than free clotrimazole against Candida albicans and Candida glabrata strains susceptible and resistant to fluconazole. Hence, clotrimazole-loaded coconut oil-core nanocapsules represent promising alternatives to the treatment of vulvovaginal candidiasis.

Clotrimazole-loaded Eudragit® RS100 nanocapsules: preparation, characterization and in vitro evaluation of antifungal activity against Candida species.

Clotrimazole is a common choice for the treatment of vulvovaginal infections, but its low solubility and some side effects pose a challenge to its application. This work evaluated the feasibility to formulate clotrimazole-loaded cationic nanocapsules using Eudragit® RS100 and medium chain triglycerides as polymer and oily core, respectively, by the method of interfacial deposition of a preformed polymer. The physicochemical characteristics of nanocapsule formulations were evaluated at 0 day and 60 days after preparation. Particle size, zeta potential, polydispersity index, pH and drug content were stable during this period. In addition, nanocapsules were able to protect clotrimazole from photodegradation under UV radiation. By the dialysis bag diffusion technique, the nanosized formulations showed prolonged release of clotrimazole by anomalous transport and first order kinetics. A microbiological study was carried out by the microdilution method and showed that nanocapsules (mean size: 144 nm; zeta potential: +12 mV) maintained the antifungal activity of clotrimazole against Candida albicans and Candida glabrata strains susceptible and resistant to fluconazole.