盐酸普萘洛尔渗透泵片的制备及Beagle犬体内药动学研究

Preparation of propranolol hydrochloride osmotic pump controlled release tablets and their pharmacokinetics in Beagle dogs

目的：制备盐酸普萘洛尔渗透泵片，对服用渗透泵片的Beagle犬进行体内药动学研究并对体外释放和体内吸收的相关性做出评价。方法：以紫外分光光度计测定自制盐酸普萘洛尔渗透泵控释片的体外释放浓度，利用反相HPLC法测定不同时间Beagle犬血浆中的药物浓度，用DAS2．0统计软件计算有关药动学参数，Wanger-Nelson法计算体内吸收百分数，并与相应时间体外累积释放百分率线性回归，进行体内外相关性评价。结果：渗透泵体外恒速释药24h累积释放90％以上，渗透泵片与普通片主要药动学参数分别为Tmax（6．617±0．754）和（3．000±0．632）h；t1/2（6．518±2．923）和（3．214±0．584）h；Cmax（259．202±32．206）和（749．582±55．402）ng·mL^-1；AUC 0-∞（2543．043±361．971）和（2708．350±385．545）ng·h·mL^-1，且体内外相关性较好。结论：渗透泵控释片血药浓度平稳，与普通片相比可较长时间保持有效血药浓度。

Objective：To prepare propranolol hydrochloride osmotic pump controlled release tablets, and investigate its pharmacokinetics in Beagle dogs and in vitro-in vivo correlation. Methods：In vitro drug release was determined by UV spectrophotometer. Serum concentration of propranolol hydrochloride in conventional tablets and osmotic pump tablet（OPT） administrated orally was determined by method. Pharmacokinetic parameters were calculated using DAS 2.0 software,and the correlation was studied by in vitro dissolution and in vivo pharmacokinetics with Wanger-Nelson method. Results：In vitro accumulative release dissolution was over 90% in 24 h. Main pharmacokinetic parameters of conventional tablet and OPT were obtained respectively ： Tmax （6. 617 ±0. 754 ） and （3. 000± 0. 632）h;t1/2 （6. 518 ±2. 923） and（3. 214±0. 584） h; Cmax （259. 202± 32. 206） and （749. 582 ± 55. 402） ng·mL^-1 AUC0 -∞ （2 543. 043 ± 361.971 ） and （2 708. 350 ±385. 545 ） ng· h· mL ^- 1. Conclusion： Plasma drug concentration of propranolol hydrochloride osmotic pump controlled release tablet was steady. Effective plasma drug concentration kept a longer time compared with that of conventional tablet.