盐酸曲马多微球缓释片的制备及药动学研究

目的 探讨盐酸曲马多微球缓释片的制备方法，并对微球缓释片在家犬体内药动学进行研究。方法 以乙基纤维素作为包裹材料，运用喷雾干燥法制备盐酸曲马多缓释微球，直接压片得到盐酸曲马多微球缓释片。对微球缓释片和市售缓释片进行家犬体内单剂量给药实验，建立高效液相分析方法。结果 HPLC显示方法精密度、回收率、专属性都符合要求。市售缓释片和微球缓释片的药动学参数C_max分别为(322±16)ng·mL^-1和(346±11)ng·mL^-1；T_max分别为(2.5±0.3)h和(1.5±0.4)h；t_1/2分别为(4.31±0.84)h和(4.95±0.79)h，AUC_0→t分别为(2 940.8±32.1)ng·h·mL^-1和(3 560.9±18.6)ng·h·mL^-1，相对生物利用度为121.09%，不同释放时间点，盐酸曲马多微球缓释片的体内吸收与体外释放都具有良好的相关性。结论 盐酸曲马多微球缓释片具有缓释效果。

Study on Preparation and Pharmacokinetics of Tramadol Hydrochloride Microspheres Sustained Release Tablets

OBJECTIVE To study the method that how to prepare tramadol hydrochloride microspheres sustained release tablets, and pharmacokinetics and relative bioavailability of microspheres sustained release tablets in dogs. METHODS EC was selected as the preparation of material. Tramadol hydrochloride microspheres sustained release tablets were prepared by the spray drying method, direct tabletting. The microspheres sustained release tablets and commercial tablets in dogs were performed in single dose experiments by HPLC. RESULTS The pharmacokinetic parameters for the single dose of the microspheres sustained release tablets and commercial tablets were as follows: C_max (322±16)ng·mL^-1 and (346±11)ng·mL^-1; T_max (2.5±0.3)h and (1.5±0.4)h; t_1/2 (4.31±0.84)h and (4.95±0.79)h, AUC_0→t (2 940.8±32.1)ng·h·mL^-1 and (3 560.9±18.6)ng·h·mL^-1, the relative bioavailability was 121.09%. CONCLUSION Tramadol hydrochloride microspheres sustained release tablets has a sustained- release effect.