盐酸洛美沙星耳用温敏原位凝胶的制备与药效学评价

Preparation and pharmacodynamic evaluation of Lomefloxacin Hydrochloride otic thermosensitive in-situ gel

目的制备盐酸洛美沙星耳用温敏原位凝胶,并评价其对豚鼠中耳炎的抑菌效果。方法使用冷溶法制备盐酸洛美沙星耳用温敏原位凝胶,分别考察不同浓度泊洛沙姆188和泊洛沙姆407对胶凝化温度的影响,并以凝胶化温度作为评价指标,通过中心复合设计-效应面法优化处方。最后比较了盐酸洛美沙星耳用温敏原位凝胶与滴耳液对豚鼠中耳炎的抑菌效果。结果经实验优化得到盐酸洛美沙星耳用温敏原位凝胶的最佳处方为:泊洛沙姆188浓度为6%(w/v),泊洛沙姆407浓度为24%(w/v);凝胶化温度为(32.6±0.6)℃。盐酸洛美沙星耳用温敏原位凝胶对豚鼠中耳炎的抑菌效果优于盐酸洛美沙星滴耳液。结论本研究制备的盐酸洛美沙星耳用温敏原位凝胶具有良好的温度敏感性,可以减慢释药速率,减少用药次数,能够提高对豚鼠中耳炎的抑菌效果,有望成为治疗中耳炎的新型给药制剂。

Objective To prepare Lomefloxacin Hydrochloride otic thermosensitive in-situ gel and evaluate its antimicrobial effect on otitis media in guinea pigs.Methods The cold-water-dissolving method was used to prepare Lomefloxacin Hydrochloride otic thermosensitive in-situ gel.The effects of poloxamer 188(PXM-188)and poloxamer 407(PXM-407)with different concentrations on the gelatinization temperature was explored.With the gelatinization temperature as the evaluation indicator,the formula was optimized through the central composite design-response surface methodology.In the end,a comparison was made between the Lomefloxacin Hydrochloride otic thermosensitive in-situ gel and Lomefloxacin Hydrochloride ear drops regarding their antimicrobial effects on otitis media in guinea pigs.Results After experimental optimization,the optimal formula of Lomefloxacin Hydrochloride otic thermosensitive in-situ gel was as follows:6%(w/v)PXM-188;24%(w/v)PXM-407;gelatinization temperature:(32.6±0.6)℃.The Lomefloxacin Hydrochloride otic thermosensitive in-situ gel was superior to Lomefloxacin Hydrochloride ear drops in antimicrobial effect on otitis media in guinea pigs.Conclusion Lomefloxacin Hydrochloride otic thermosensitive in-situ gel prepared in this study is temperature-sensitive,which can slow down the rate of drug release,reduce the frequency of drug administration,and improve the antibacterial effect on otitis media in guinea pigs.It is expected to be a new drug preparation for the treatment of otitis media.