尼美舒利缓释栓的制备与药动学研究  

Preparation and Pharmacokinetics of Sustained Release Suppositories of Nimesulide

作　　者：陈永顺[1] 吕明[1] 王启斌[1] 杜士明[1] 董永成[1] 

机构地区：[1]郧阳医学院附属太和医院药学部,湖北十堰442000

出　　处：《医药导报》2009年第9期1194-1197,共4页Herald of Medicine

摘　　要：目的研制尼美舒利缓释栓,为临床提供一种维持时间长、用药方便和不良反应小的尼美舒利制剂,并考察其释放度和药动学。方法以PEG400、PEG4000为主要基质,阻滞剂Eudragit RL100及硬脂酸,采用正交设计法,以体外释放度为指标,优化尼美舒利缓释栓处方。体外释放度采用《中华人民共和国药典》2005版二部转篮法,体内血药浓度用高效液相色谱(HPLC)法测定和3P97程序计算药动学参数。结果当PEG400:PEG4000为40:60,EudragitRL100、硬脂酸、吐温80含量分别为0.5%,1.5%,1.0%时,体外释药行为符合Higuchi方程;体内过程为一室模型,药动学参数为t1/2=(1.9±0.5)h,tpeak=(2.5±0.7)h,Cmax=(11.5±2.7)μg.mL-1,AUC0→24=(85.5±13.1)μg.L-1.h,相对生物利用度为(102.2±13.5)%。结论该制剂与普通栓相比,达峰浓度降低,达峰时间延长,缓释特征明显。Objective Sustained release suppositories of nimesulide were prepared to provide a new preparation of nimesulide with prolonged action, fewer side effects for clinic use. The drug release rate and pharmacokinetic parameters were also investigated. Methods Optimized the forumlation of sustained release suppositories of nimesulide by using PEG400 and PEG4000 as main matrices, Eudragit RLI00 and stearate as sustained materials, orthogonal design method to dealing with data, and drug release of nimesulide in vitro as marker. The rate of drug release was determined according to Volume II of the Chinese Pharmacopoeia 2005. The blood concentration of drug was tested by HPLC, the pharmacokinetic parameters of nimesalide were calculated with 31：97 program software. Results The drug release pattern in vitro was consistent with Higuchi equation and nimesulide in vivo fit to one-compartment model with PEG400 ： PEG4000 at the ratio of 40 ： 60, contents of Eudragit RL100, stearic acid, tween 80 being 0.5 % , 1.5 % , 1.0%, respectively. The pharmacokinetic parameters were as follows, t1/2 = （ 1.9 ± 0.5 ） h, tpeak = （2.5±0.7 ） h, Cmax = （ 11.5 ＋ 2.7 ）μg·mL-1, AUC0→24h = （ 85.5 ± 13. 1 ） μg ·L-1· h . And the relative bioavailability was （ 102.2 ± 13.5） %. Conclusion Compared with common preparations, the sustained release suppositories of nimesulide have a lower peak level, longer time to reach peak concentration and extended sustained release characteristics.

关 键 词：尼美舒利 缓释栓 释放度 药动学 

分 类 号：R971.1[医药卫生—药品] TQ460.6[医药卫生—药学]