酒石酸罗格列酮缓释胶囊的制备及其体内外评价  

Preparation and in vitro and in vivo investigation of Rosiglitazone tartrate sustained release capsules

作　　者：刘洋[1,2] 陈小让[1] 胡玉荣[1] 张振中[1] 

机构地区：[1]郑州大学药学院,河南郑州450001 [2]沈阳药科大学,辽宁沈阳110016

出　　处：《华西药学杂志》2014年第6期622-624,共3页West China Journal of Pharmaceutical Sciences

摘　　要：目的制备酒石酸罗格列酮缓释胶囊,并研究其体外释药情况和在犬体内的药动学参数及相对生物利用度。方法采用挤出滚圆技术制备酒石酸罗格列酮微丸,流化床内采用丙烯酸树脂水分散体包衣,装入明胶硬质胶囊中;分别ig给予6只犬酒石酸罗格列酮缓释胶囊和市售速释胶囊,研究缓释胶囊在犬体内的药动学参数和相对生物利用度。结果自制缓释胶囊12 h内在水（pH7.0）、p H1.2、pH5.0、p H6.8条件下均有良好的缓释效果;酒石酸罗格列酮3.125～1619.6 ng·mL＾-1与峰面积的线性关系良好,检测限为0.94 ng·mL^-1;给予6只犬口服缓释胶囊和市售速释胶囊后的Tmax为3.0、1.5 h,Cmax为367.0±272.2、714.1±439.2 ng·mL^-1,AUC0-24 h为2258.4±510.0、2140.8±606.1 ng·mL＾-1,t1/2为4.5±1.3、2.2±0.7h;缓释胶囊的相对生物利用度为105.2%±2.1%。结论成功制备了酒石酸罗格列酮缓释胶囊,其体外释药缓慢、平稳,与市售参比制剂生物等效。OBJECTIVE To prepare Rosiglitazone tartrate sustained release capsules and investigate its in vitro release and in vivo pharmacokinetics and bioavailability in dogs. METHODS Extrusion- spheronization method was used to prepare uncoated pellets.Eudragit aqueous dispersion was used as a sustained release layer in a fluid bed equipment loaded in gelatin hard capsules. 6 dogs were intragastrical administration Rosiglitazone sustained release capsules and immediate release capsules saled in market. In vitro release of the drug from the pellets was studied. The pharmacokinetic parameters and relative bioavailability of Rosiglitazone tartrate sustained release capsules and immediate release capsules in the dogs were studied. RESULT The sustained release capsules showed a slow and steady release in water,p H1. 2,p H5. 0 and p H6. 8. The plasma concentration measured were liner from 3. 125- 1619. 6 ng·m L^- 1. The lowest limit of quantification was 2. 343 ng·m L^- 1. 6 dogs were administered rosiglitazone tartrate sustained release capsules and immediate release capsules. The main pharmacokinetic parameters in the sustained release capsules were： Tmax3. 0 h,Cmax367. 0 ± 272. 2 ng·m L^- 1,AUC0- 24 h2258. 4 ± 510 ng·m L^- 1 and t1 /24. 5 ± 1. 3 h,and in immediate release capsules were： Tmax1. 5 h,Cmax714. 1 ± 439. 2ng·m L^- 1,AUC0- 24 h2140. 8 ± 606 ng·m L^- 1 and t1 /22. 2 ± 0. 7 h. The relative bioavailability of sustained release capsules was105. 5% ± 2. 1%. CONCLUSION The results of statistical analysis show that they were bioequivalent.

关 键 词：酒石酸罗格列酮 缓释胶囊 生物利用度 挤出滚圆 

分 类 号：R94[医药卫生—药剂学]