基于泊洛沙姆的温度敏感性原位凝胶制剂制备及体外评价.pdf

基于泊洛沙姆的温度敏感性原位凝胶制剂 制备及体外评价 学生：韩聪 指导老师：刘瑜 摘要： 目的：考察基于泊洛沙姆的温敏性凝胶作为阴道制剂的可行性。方法：以冷置溶 解法制备泊洛沙姆凝胶（PH）及泊洛沙姆/卡拉胶凝胶（CPH），并进行苦参碱、奥硝唑等模型 药物的载药，建立载药温敏凝胶的鉴定方法和 HPLC 定量方法，测定不同处方凝胶的流变学参 数对温度的敏感性，采用无膜释放法考察凝胶溶蚀及药物释放，并对部分处方进行 1 年稳定性 考察。结果：载苦参碱的 PH 均具有显著的温度敏感性和较好的稳定性。CPH 在保持了 PH 温敏 性的同时，具有显著的钾离子敏感性。CPH 经溶蚀后温敏性逐渐减弱。CPH 本身含有的钾离 子、钠离子和较高浓度 pH7.0 的 PBS(≥20mM)会加速凝胶溶蚀。奥硝唑从含有不同缓冲盐浓度 的 CPH 中的释放符合 Ritger-Peppas 方程，释放机制以药物扩散为主。结论：基于泊洛沙姆的 温敏性凝胶在阴道给药方面具有很好的应用前景。 关键词：温敏凝胶 流变学 凝胶溶蚀 影响因素 体外释药 Abstract: Objective ：To investigate the potential of poloxamer-based thermosensitive hydrogel as vaginal formulations. Methods: “Cold method” was used to prepare poloxamer hydrogel (PH) and poloxamer/carrageenan(CPH) and model drugs like matrine and ornidazole were loaded in PH and CPH respectively. Identification and HPLC quantitative methods were established and rheology of hydrogels was measured. The membrane-less method was used to monitor the hydrogel erosion and drug release. 1 year stability of some formulations was also evaluated. Results: Matrine-loaded PH had obvious thermosensitivity and good stability. Besides thermosensitivity, CPH showed significant sensitivity to potassium. After erosion CPH gradually lost thermosensitivity. Cations contained in CPH also changed the erosion profiles. Release of ornidazole from CPH followed Ritger-Peppas equation, demonstrating the prevalent contribution of drug diffusion. Conclusion: Poloxamer-based thermosensitive hydrogel shows good potential as vaginal formulations. Key words: thermosensitive in-situ gel; rheology; gel erosion; influencing factors; drug release in vitro 引言 阴道给药系统主要用于局部给药，少数情况下也用于全身给药。由于阴道给 药是妇科疾病防治的重要途径，故研究给药方便、生物利用度高的阴道给药系统很 有必要。在本实验中，我们考察了基于泊洛沙姆的温敏性凝胶作为阴道制剂的可行 性，包括以冷置溶解法制备泊洛沙姆凝胶（PH）及泊洛沙姆/卡拉胶凝胶（CPH）， 并进行苦参碱、奥硝唑等模型药物的载药，建立载药温敏凝胶的鉴定方法和HPLC 定量方法，测定不同处方凝胶的流变学参数对温度的敏感性，采用无膜释放