Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Egypt.
Acta Pharm. 2012 Mar;62(1):59-70. doi: 10.2478/v10007-012-0009-y.
The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (T(gel)), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The T(gel) decreased with increasing PF-127 concentration. The T(gel) was modulated by addition of PF-68 to be within the acceptable range of 25-37 °C. With increasing pluronic concentration, the in vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.
本研究旨在开发甲硝唑（MTZ）的基于泊洛沙姆的原位凝胶制剂，用于治疗细菌性阴道病，旨在延长滞留时间、控制药物释放、增强疗效、减少复发和提高患者依从性。原位凝胶制剂是使用不同浓度的泊洛沙姆 F-127（PF-127）单独和与泊洛沙姆 F-68（PF-68）组合制备的。对制备的制剂进行了胶凝温度（T（凝胶））、体外药物释放、流变学特性、粘膜粘附性和组织水平阴道粘膜耐受性的评价。T（凝胶）随 PF-127 浓度的增加而降低。通过添加 PF-68 将 T（凝胶）调制到可接受的 25-37°C 范围内。随着泊洛沙姆浓度的增加，体外药物释放减少，粘度和粘膜粘附力增加。来自对照组和治疗组的兔阴道的组织病理学检查显示阴道和宫颈的组织学正常。基于对制备制剂的体外评价，选择含有 PF-127/PF-68（20/10％，m/m）的原位凝胶液体进行进一步的临床评价。
