氢溴酸高乌甲素鼻用原位凝胶剂的制备及其处方评价

An in Situ Gel System for Nasal Delivery of Lappaconitine Hydrobromide:Preparation and Formulation Evaluation

目的:制备氢溴酸高乌甲素(LH)鼻用原位凝胶剂,并进行处方考察以提高其鼻腔给药的镇痛效果。方法:采用在体蟾蜍上腭纤毛法考察不同LH处方对鼻黏膜纤毛的毒性、大鼠在体鼻腔循环实验考察处方中3种吸收促进剂(β-环糊精、吐温-80和冰片)对LH的鼻黏膜吸收的促进作用以及小鼠扭体法实验考察不同LH处方的镇痛药效,从而确定LH鼻用原位凝胶剂的最佳处方工艺。结果:处方中LH和所选用的辅料对鼻黏膜纤毛均无显著毒性;3种吸收促进剂对LH的鼻黏膜吸收速率常数无显著影响(P>0.05);在所有受试处方中,结冷胶和β-环糊精联用处方制剂的镇痛效果最佳,其药效与腹腔注射相同剂量的LH注射液无显著差异(P>0.05)。结论:结冷胶和β-环糊精联用是制备LH鼻用原位凝胶剂的最佳处方组合。

Objective： To prepare an in situ gel system for nasal delivery of lappaconitine hydrobromide （LH） and to evaluate the analgesic effect of its formulation. Methods： The nasal mucocilia toxicities of different LH formulations were observed using in situ toad palate model, the absorption-enhancing effects of three absorption enhancers, β-CD, Tween-80 and Borneol, on nasal mucosa absorption of LH were measured by in situ rat nasal circulation perfusion test, and the analgesic effects of different LH formulations were measured by the mouse writhing test, so as to find the optimal formulation and preparation procedure of in situ gel system for nasal delivery of LH. Results： Both LH and the used excipients showed no significant effect on nasal mucocilia movement. The three absorption enhancers induced no significant change of the nasal mocusa absorption rate constant of LH （ P 〉 0.05）. The in situ gel system prepared with gellan gum and β-CD showed the best analgesic effect among all the selected formulations, which had no significant difference from that of LH intraperitoneal injection at the same dose （ P 〉 0.05）. Conelusion： The in situ gel system with gellan gum and β-CD is the optimal formulation for nasal delivery of LH.