Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole: β-cyclodextrin complex

The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility., clotrimazole was incorporated as its inclusion complex with 1∶1 molar ratio with β-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including 1H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k1∶1). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with β-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug: cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole: β-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values

Nanoformulations for drug delivery: safety, toxicity, and efficacy

This chapter presents an outline of the recent available information regarding safety, toxicity, and efficacy of nano drug delivery systems. Of particular importance is the evaluation of several key factors to design nontoxic and effective nanoformulations. Among them, we focus on nanostructure materials and synthesis methods, mechanisms of interactions with biological systems, treatment of nanoparticles, manufacture impurities, and nanostability. Emphasis is given to in silico, in vitro, and in vivo models used to assess and predict the toxicity of these new formulations. Additionally, some examples of in vitro and in vivo studies of specific nanoderivatives are also presented in this chapter