布地奈德灌肠用温敏性凝胶的体外释放度及局部滞留性评价

目的:考察布地奈德灌肠用温敏性凝胶的体外释放度及体内滞留性。方法:制备布地奈德温敏凝胶灌肠液,采用动态透析法和高效液相色谱法进行体外释放度研究;以新吲哚菁绿IR820为荧光标记物,昆明小鼠为受试动物,应用小动物活体成像系统检测不同时间点温敏凝胶灌肠液在小鼠体内的滞留情况。结果:含有增溶剂的布地奈德温敏凝胶灌肠液在体外能缓慢并完全地释放,体外释药曲线符合Higuchi方程,12 h释放在80%以上,普通灌肠液12 h的累积释药率不到60%;通过对新吲哚菁绿标记物观察,温敏凝胶剂在体内至少可以停留12 h,普通灌肠液体内4 h时几乎不能观察到荧光信号。结论:布地奈德温敏凝胶灌肠液可延长药物在体内的滞留时间,延缓药物释放。

Evaluation of in vitro release and local retention of temperature-sensitive gel for budesonide enema

OBJECTIVE To investigate the in vitro release and retention of the thermo-sensitive gel for budesonide enema. METHODS Budesonide thermo-sensitive gel enema was prepared and the in vitro release rate was determined by dynamic dialysis and high performance liquid chromatography. Caliper IVIS Lumina Ⅱ was applied to evaluate the retention of budesonide thermosensitive gel in MK mice with IR820 as the fluorescent marker. RESULTS The budesonide temperature-sensitive gel enema containing solubilizer can slowly and completely released in vitro, in which the in vitro release curve accords with the Higuchi equation, and the release rate is above 80% at 12 h, and the cumulative release rate of common enema solution at 12 h is below 60%. The thermo-sensitive gel could remain in vivo for at least 12 h by observing the new indocyanine green marker, while common enema could hardly be detected in the body for 4 hours. CONCLUSION Budesonide thermosensitive gel enema can prolong the retention time of drugs and delay drug release.