奥美拉唑肠溶片的研制及其体内外评价

Preparation and in vitro/in vivo Evaluation of Omeprazole Enteric-coated Tablets

制备奥美拉唑肠溶片并测定其体外释放度,考察其在Beagle 犬体内的药动学特征。采用湿法制粒制备含药颗粒,与外加辅料混合均匀后压片,依次包隔离层和肠溶衣层,制得含奥美拉唑10 mg 的肠溶片。以奥美拉唑镁肠溶片(洛赛克,10 mg)为参比制剂,进行体外释放和Beagle 犬体内药动学的对比试验。结果显示,自制制剂和参比制剂的体外释放曲线相似因子(f2)计算值为86.17,因此判定二者的体外释放行为相似。自制与参比制剂在犬体内的AUC0→12 h、tmax 和cmax 分别为(2.40±0.52)和(2.51±0.54)h·mg·L^-1、(1.83±0.16)和(1.90±0.13) h、(1.05±0.15)和(1.05±0.12)mg/L;经配对t 检验分析,两制剂间的tmax 和cmax 没有显著性差异(P>0.05)。自制肠溶片的相对生物利用度为(96.60±14.18)%。

The formulation of omeprazole enteric-coated tablets was optimized by single factor test, then the in vitro release and pharmacokinetics in Beagle dogs were investigated with Losec MUPS (10 mg) as reference preparation in this paper. The drug-loaded granules were prepared by wet granulation, followed by mixing evenly with additional excipients, then the mixture was compressed to obtain the tablet cores. The title tablets containing 10 mg of omeprazole were obtain by coating isolation layer and enteric layer successively. According to the results of in vitro release of selfmade and reference tablets, the similarity factor (f2) was calculated and the result (f2=86.17) indicated the similarity between release profiles of the two preparations. Furthermore, the pharmacokinetic characteristics of self-made and reference preparations in Beagle dogs were compared. The AUC0→12 h, tmax and cmax of the self-made and reference entericcoated tablets were as follows:(2.40±0.52) and (2.51±0.54)h·mg·L-1,(1.83±0.16) and (1.90±0.13)h,(1.05±0.15) and (1.05±0.12)mg/L, respectively. The paired t test showed that there were no significant differences in pharmacokinetic parameters between the self-made and reference preparations (P>0.05). The relative bioavailability of self-made preparation was (96.60±14.18)%.