摘要
目的:以进口制剂为参比,考察自制硝苯地平控释片体外药物释放特征和体内药动学。方法:分别采用4种不同pH缓冲溶液作为释放介质,并对pH6.8释放介质分别采用3种不同转速来测定硝苯地平控释片体外药物释放度,考察释放介质pH和转速对释放度的影响。采用气相色谱法(GC)测定健康男性受试者口服硝苯地平控释片后体内血药浓度。结果:硝苯地平控释片在不同pH释放介质中的释放度一致,均符合零级动力学,且不受转速的影响。单剂量口服后,自制制剂和进口制剂主要药动学参数分别为:t1/2β(13.0±4.4)h和(12.7±4.7)h;tmax(14.2±7.8)h和(16.7±7.6)h;Cmax(29.3±10.2)μg.L-1和(25.6±8.1)μg.L-1;AUC0-60(778.2±298.1)μg.L-1.h和(735.5±261.3)μg.L-1.h;AUC0-∞(834.3±334.1)μg.L1.h和(798.8±283.6)μg.L1.h。相对于进口制剂,自制制剂相对生物利用度F(AUC0-60)为(106.4±17.0)%,F(AUC0-∞)为(105.4±18.2)%。2种制剂的Cmax、AUC0-60、AUC0-∞及tmax差异无显著性。结论:硝苯地平控释片体外药物释放不受释放介质pH和转速的影响;自制制剂与进口制剂生物等效。
OBJECTIVE To study the drug release characteristics in vitro and the pharmacokinetic properties in vivo of self- made nifedipine controlled release tablets using the imported preparation as the reference. METHODS To study the effect of pH value of media on the drug release characteristic of nifedipine controlled release tablets, four types of release media with dif ferent pH values were used respectively. And for the release media of pH 6. 8, three rotating speeds were taken to study its effect on the drug release. The blood drug concentrations of healthy male volunteers after administration with a single-dose of 30 mg nifedipine controlled-release tablet were determined by method of GC. RESULTS The drug release profiles in different media with various pH values were similar, and the drug release was of zero-order kinetics. The drug release was not affected by the rotating speed within the range studied. The main pharmacokinetic parameters of the self-made preparation and the imported preparation after single dose administration were as follows： t1/2β （ 13.0 ± 4. 4） h and （ 12.7 ± 4. 7） h; tmax （ 14. 2 ± 7. 8） h and （ 16. 7 ± 7. 6） h; Cmax （29. 3 ± 10. 2 ） μg.L-1 and （25.6 ± 8. 1 ） μg. L-1~ ; AUC0-60 （778. 2 ± 298. 1 ） μg. L- 1 h and （ 735. 5 ± 261.3） μg.L-1 .h;AUC0-∞ （834. 3 ± 334. 1） μg. L-1 .h and （798.8 ± 283. 6） μg. L -1.h. The relative bioavailability of the self-made preparation versus the imported preparation was as follows：F（AUC0-60） （106. 4 ± 17. 0）% and F（AUC0-∞） （105.4± 18. 2） %. There was no significant difference in Cmax ,AUG0-60 ,AUC0-∞ and tmax between the two preparations. CONCLUSION The pH values of release media and the rotating speed have no effect on the drug release. The test preparation is bioequivalent to the reference preparation.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2010年第7期553-557,共5页
Chinese Journal of Hospital Pharmacy
关键词
硝苯地平控释片
释放度
气相色谱
药动学
生物等效
nifedipine controlled-release tablets
dissolution
GC
pharmacokinetics
bioequivalenee
