赖氨酸布洛芬缓释液体栓的制备及体内外评价

Preparation of Ibuprofen Lysine Sustained-release Liquid Suppository and Its Evaluation in vivo and in vitro

目的:制备赖氨酸布洛芬缓释液体栓剂,并进行体内外评价。方法:以泊洛沙姆溶液为主要基质、卡波姆为生物黏附剂、月桂氮酮为渗透剂,制备赖氨酸布洛芬缓释液体栓剂。以胶凝温度、凝胶强度、生物黏附力及体外释放度为指标筛选泊洛沙姆407(P407)-泊洛沙姆188(P188)比例和卡波姆的含量,比较所制液体栓剂与普通固体栓剂经直肠给药后在Beagle犬体内的药-时曲线和药动学参数。结果:处方中P407-P188比例为1∶1.2时缓释液体栓剂的胶凝温度为30.4~38.1℃,最接近直肠温度;卡波姆含量为0.8%时缓释液体栓剂的体外释放符合零级方程,相关性最好(R^2=0.996)。普通固体栓的tmax为3.206 h,随后血药浓度下降明显,缓释时间不超过12 h,AUC_(0-∞)为501.826 mg·h/L;缓释液体栓剂的t_(max)为8.814 h,随后血药浓度下降,缓释时间超过24 h,AUC_(0-∞)为715.489 mg·h/L。结论:成功制得赖氨酸布洛芬缓释液体栓剂,与普通固体栓剂比较其缓控释效果更佳、体内外相关性良好。

OBJECTIVE：To prepare Ibuprofen lysine sustained-release liquid suppository,and conduct the evaluation in vivo and in vitro. METHODS：Ibuprofen lysine sustained-release liquid suppository was prepared by using Poloxamer solution as main matrix,carbomer as bioadhesive agent,laurocapram as penetrant. The ratios of poloxamer 407（P407）-poloxamer 188（P188）and carbomer content were screened by using gel temperature,gel intensity,biological adhesion and release rate in vitro as indexes,and the concentration-time curves and pharmacokinetic parameters of prepared liquid suppository and common solid suppository after rectal administration in Beagle dogs in vivo were compared. RESULTS：When the P407-P188 ratio was 1 ∶ 1.2,the gel temperature of sustained-release liquid suppository was 30.4-38.1 ℃,which was the nearest to the rectal temperature;when the content of carbomer was 0.8%,the in vitro release of sustained-release liquid suppository was in zero-order model,with favorable correlation（R^2=0.996）. The tmaxof common solid suppository was 3.206 h,then plasma concentration decreased significantly,release time did not exceed 12 h,AUC0-∞ was 501.826 mg·h/L;tmax of sustained-release liquid suppository was 8.814 h,then plasma concentration decreased,release time exceeded 24 h,AUC0-∞ was 715.489 mg·h/L. CONCLUSIONS：Ibuprofen lysine sustained-release liquid suppository is successfully prepared,which shows better sustained-release effect and excellent correlation in vivo and in vitro than common solid suppository.