注射用粉防己碱温敏型缓释原位凝胶的制备

Preparation of the temperature-sensitive sustained release in situ tetrandrine gel for injection

目的制备以泊洛沙姆407(P407)为基本材料的注射用粉防己碱温敏型缓释原位凝胶,并考察其体外溶出行为。方法采用冷溶法制备凝胶,以胶凝温度为指标,考察单独使用P407和加入其他辅料F188、PEG1500、HPMC、MC对胶凝温度的影响;采用无膜溶出法考察凝胶的体外溶蚀和释放行为,并采用HPLC测定溶出液中药物的含量,筛选较优处方。结果胶凝温度随P407浓度的增大而降低;且当P407浓度低于15%时不发生相转变,辅料F188、PEG1500、MC的加入不能制备出符合要求的凝胶;8.0%、8.5%、9.0%HPMC分别与8.0%P407混合制备凝胶的胶凝温度符合要求;HPMC浓度越高,药物释放越快,8.0%HPMC和8.0%P407混合后,胶凝温度和缓释效果均符合实验要求。结论筛选出的处方中大大降低了P407的浓度,同时胶凝温度和缓释效果均符合实验要求,该温敏性凝胶具有良好的温度敏感性,制备方法简单可行。

OBJECTIVE To prepare the temperature - sensitive sustained release in situ tetrandrine gel for injection based on polox- amer 407 （ P407 ）. METHODS The gel was prepared by the method of natural expansion. Then the effect of different concentrations of P407 on gel formation was studied and the gelling temperature was investigated by adding other excipients to various concentrations of P407. HPLC was used to study the in vitro release behavior, and the gel meets the requirements was chosen. RESULTS Gelling temperature decreased with the increment of the P407 concentration, and it did not happen when P407 concentration was below 15 % in phase transition. The addition of appendix of Fl88 ,PEG1500 and MC could not prepare the required gel. The mixure of 8.0% ,8.5% or 9. 0% HPMC with 8.0% P407 could prepare the requird gel, the higher HPMC concentration, faster the drug release. After 8.0% HPMC was mixed with 8. 0% P407, the gelation temperature and sustained release effect met the experimental requirements. CONCLUSION The optimized formulation adopted greatly reduced concentration, and both the gelation temperature and sustained realcase effect met the requirement. The prepared temperature - sensitive gel has good sensitivity to temperature and the preparation method is easy to operate.