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

Abstract

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 1 H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k 1:1 ). 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.

Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis

“…Formulations G 1 and G 2 containing suspended curcumin (1% and 2%) showed higher gelation temperature (34 C) than G 3 and G 4 containing curcumin dissolved in PEG400 1% and 2% showing gelation temperature (30 C and 28 C, respectively) in spite of using the same concentration of thermosensitive polymer (30% pluronic F127) in all formulations, this might be due to the presence of PEG400 added to solubilize curcumin. These results were in agreement with observation of Bilensoy et al who reported that the gelation temperature of pluronic in-situ gel of clotrimazole decreased upon using of PEG400 as a solubilizing agent and an excess amount of PEG causes the formation of gels even at 4 C (Bilensoy et al, 2006). Formulation G 5 containing curcumin dissolved in ethanol did not form gel at body temperature 37 C which was previously observed by Dumortier et al who reported that ethanol reduce the gel strength and bioadhesive force and increase Tsol-gel (Dumortier et al, 2006).…”

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

“…1 These have an extensive range of applications in the medical field such as drug solubilization, controlled drug release. [2][3][4] Moreover, Pluronic have recently attracted a great deal of attention as excellent membrane sealants with low toxicity. [5][6][7] Of particular interest is poloxamer 188 (Pluronic F68), an approximately 8400 g/mol poloxamer of the form PEO 76 -PPO 29 -PEO 76 that has been proven as a surfactant sealing agent for permeabilized lipid bilayers.…”

pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

“…It has been reported previously that the rate of dissolution of gel is actually the controlling factor in drug release. 16 In this respect, the gel pH-sensitive pattern would explain the constant release at pH 5.0.…”