A thermosensitive vaginal gel formulation with HP gamma CD for the pH-dependent release and solubilization of amphotericin B

作者：Kim Ye Tae; Shin Baek Ki; Garripelli Vivek Kumar; Kim Jin Ki; Davaa Enkhzaya; Jo Seongbong; Park Jeong Sook^*

来源：European Journal of Pharmaceutical Sciences, 2010, 41(2): 399-406.

DOI：10.1016/j.ejps.2010.07.009

• Amphotericin B
• HP gamma CD
• pH-sensitive polymer
• pH-dependent degradation
• Vaginal gel
• Novel copolymer

To achieve better therapeutic efficacy and patient compliance in the treatment for Candida vaginitis, the antifungal agent amphotericin B (AmB) was formulated in a vaginal gel using Pluronic (R)-based multiblock copolymers (MBCP-2). To increase its aqueous solubility, the drug was incorporated as its inclusion complex with hydroxypropyl-gamma-cyclodextrin (HP gamma GD). The formation of the AmB inclusion complex was characterized using different techniques including XRD, FT-IR spectrophotometry, DSC, and SEM. The sol-gel transition diagrams were determined by the inversion method at temperature intervals of 2 degrees C. Moreover, a histopathology study was performed to determine whether vaginal tissue damage was caused by repeated doses. The inclusion complex between AmB and HP gamma CD was completely formed, and the aqueous solubility of AmB was improved by the formation of the inclusion complex. The sol-gel transition diagrams showed that the aqueous solutions of MBCP-2 gelled at body temperature, and the gelation temperature of the polymer solutions was dependent on polymer concentration. In vitro drug release results indicated that MBCP-2 exhibited a sustained release of AmB in pH 7.4 and pH 9.0 buffers, whereas at pH 5.0, it presented a constant release that was completed within 3 days. There was no visible sign of inflammation or necrosis in vaginal tissues after repetitive intravaginal application. In conclusion, the thermosensitive vaginal gel might be useful in the delivery of an antifungal agent for local treatment.

• 出版日期2010-10-9