盐酸曲马多控释片的制备及犬体内生物利用度研究

Preparation of tramadol hydrochloride controlled-release tablets and evaluation of its bioavailability in dogs

目的：制备盐酸曲马多控释片,研究其在犬体内的相对生物利用度。方法：以乙酸纤维素为包衣材料,以聚乙二醇400为致孔剂,制备每日给药2次的盐酸曲马多控释片;用HPLC法测定家犬单剂量交叉经口给药200 mg市售普通片和自制控释片后血浆中盐酸曲马多的浓度。结果：犬体内普通片与控释片的AUC0～∞分别为（10 230.6±2 312.1）和（10 808.8±1 794.3）ng·h·mL^-1;Cmax分别为（1 670.6±252.3）和（812.7±94.3）ng·mL^-1;Tmax分别为（2.0±0.4）和（7.5±1.9）h。结论：自制控释片在犬体内具有良好的控释效果,相对生物利用度为（107.0±8.2）%;体内外相关性良好。

Objective：To prepare tramadol hydrochloride controlled-release tablets and to evaluate its relative bioavailability in dogs. Methods：Tramadol hydrochloride controlled-release tablets were prepared with cellulose acetate as coating materials, polyethylene glycol 400 as pore-forming agents. In a randomized, crossover, and single-dose study, the tramadol concentration in dog plasma was measured by HPLC after an oral administration of 200 mg commercial conventional tablets or controlled-release tablets. Results： The pharmacokinetic parameters were as follows, AUC0-∞ （ 10 230.6 ± 2 312.1 ） and （ 10 808.8 ± 1 794.3 ） ng· h· mL^-1 , Cmax （ 1 670.6 ± 252.3 ） and （812.7 ± 94.3 ） ng· mL^-1, Tmax （2.0 ± 0.4） and （7.5 ±1.9 ） h, for conventional and controlled-release tablets respectively. Conclusion：Tramadol hydrochloride controlled-release tablets had well controlled-release characteristics in vivo, and the relative bioavailability was（ 107.0 ± 8.2） %. Furthermore, the correlation of pharmacokinetics in vivo and release in vitro was good for controlled-release tablets.