美沙拉嗪直肠原位温敏凝胶的制备及体外评价

Preparation and in vitro evaluation of mesalazine thermosensitive in situ gel for rectum

目的:优选具有温敏性和直肠滞留黏附性能的美沙拉嗪原位温敏凝胶。方法:通过冷法制备,以胶凝温度为指标,采用星点设计-效应面法,对泊洛沙姆407(poloxamer 407,P407)、泊洛沙姆188(poloxamer 188,P188)以及羟丙基甲基纤维素(hydroxy propyl methyl cellulose,HPMC)的用量进行优选,通过大鼠直肠给药考察其直肠滞留情况,并以改良桨法考察体外释放度。结果:确定的最优处方为美沙拉嗪6. 7%,HPMC 0. 42%,P188 3. 46%,P407 18. 11%,苯扎溴铵0. 02%。该处方凝胶在大鼠直肠给药后不会出现泄漏,且能在体内滞留6 h以上,其体外释放符合Weibull模型。结论:优选得到符合直肠给药需求的美沙拉嗪原位温敏凝胶。

Objective:To optimize the prescription of mesalazine in situ gel with thermosensitive and rectal retention properties.Methods:Thermosensitive gel was prepared by cold method,and then taking gelation temperature as an indicator,central combination-response surface method was used to optimize the dosages of poloxamer 407(P407),poloxamer 188(P188)and hydroxy propyl methyl cellulose(HPMC).The rectal retention was investigated by rectal administration in rats,and the release rate was investigated by modified paddle method.Results:The optimal formulation was composed of mesalazine 6.7%,HPMC 0.42%,P188 3.46%,P407 18.11%,and benzalkonium bromide 0.02%.The formulated gel showed no leakage after rectal administration in rats and was able to stay in the body for more than 6 h.Its in vitro release was in line with the Weibull model.Conclusion:The established optimal prescription can obtain mesalazine in situ thermosensitive gel that meets the requirements of rectal administration.