盐酸曲马多缓释栓的研制及其药动学

Study on sustained release suppositories of tramadol hydrochloride and its human pharmacokinetics

目的 :研制盐酸曲马多缓释栓 ,以期为临床提供一种起效快、维持时间长、用药方便的新型盐酸曲马多制剂。方法 :以壳聚糖及丙烯酸树脂III号为成囊及缓释材料 ,制备盐酸曲马多微囊 ,结合中空栓技术研制包含速释、缓释两部分的缓释栓 ,对其体外溶出特征、健康自愿者体内药动学特性及两者的相关性作了研究 ,并与普通栓、普通中空栓及进口曲马多栓比较。结果 :盐酸曲马多控释栓体外溶出呈一级过程 ,K0 -1=2 4 .6h-1,显速效 ,K2 -12 =2 .0 4 6 4h-1,显缓释作用 ,体内药动学基本参数分别为t1/ 2Ka=(1.1± 0 .8)h ,t1/ 2 β=(8.8± 1.8)h ,AUC0→∞ =(36 0 1± 30 4 ) μg·L-1·h ,体内外释药相关性显著 (P <0 .0 1)。结论 :本品奏效迅速 ,维持时间长 ,血药浓度平坦 ,生物利用度高。

OBJECTIVE To study sustained release suppositories of tramadol hydrochloride in order to provide a new preparation of tramadol with quicker effect, prolonged effective time for clinic. METHODS The preparation was made with encapsulation technology connected with hollow suppositories method, using chitosan and acrylic acid resin III as sustained release materials. Contrasted with common suppositories and common hollow suppositories, the drug release pattern in-vitro , in-vivo and the relativity between them of the preparation were also studied, Its stability in-vitro was determined by accelerated testing. RESULTS The drug release pattern in-vitro of the preparation was well described by first-order kinetics and had excellent relativity with that of in-vivo . The pharmacokinetic parameters t _ 1/2 Ka , t _ 1/2β , T _ max , C _ max and AUC_ 0→∞ were ( 1.1 ± 0.8 )h, ( 8.8 ± 1.6 )h, ( 3.2 ± 1.3 )h, (165±36) μg·L -1 ·h and (3601±324) μg·L -1 ·h respectively. They had significant difference with those of common suppositories ( P < 0.01 ). The in-vitro stability of the preparation was good. CONCLUSION The sustained release suppositories of tramadol hydrochloride was promising with higher bioavaibility and flatter plasma concentration. It was valuable to be further studied as a new preparation of tramadol.