替格瑞洛原料药粒径对其片剂体外溶出行为的影响

Effects of Particle Size of Ticagrelor Crude Drug on in vitro Dissolution Behavior of Ticagrelor Tablets

目的:研究替格瑞洛原料药粒径对其片剂体外溶出行为的影响。方法:取替格瑞洛原料药及其经粉碎不同时间(15、30、40、60 s)后得到的不同粒径的粉末A、B、C、D、E,以湿法制粒法制备成片剂;采用紫外分光光度法在300 nm波长处测定上述各自制片在60 min内的体外累积溶出度(以0.2%聚山梨酯溶液为溶出介质,桨法),并以原研片为参比制剂,用相似因子(f2)法比较5种自制片与原研片体外溶出行为的相似性。结果:粉末A、B、C、D、E的d(0.9)分别为69.181、40.778、24.805、12.611、3.083μm,f2值分别为27.77、36.79、50.06、67.68、79.99。结论:替格瑞洛原料药粒径越小,所制片剂溶出行为越接近原研片。原料药经粉碎后可显著提高替格瑞洛片的体外溶出度。为获得与原研片生物等效的制剂,建议替格瑞洛原料药粉末粒径分布宜控制在d(0.9)≤20μm。

OBJECTIVE：To study the effects of particle size of ticagrelor crude drug on in vitro dissolution behavior of Ticagrelor tablets. METHODS：Ticagrelor crude drug and different particle size of ticagrelor powder A,B,C,D,E after smashing for different time（15,30,40,60 s）were used to prepare the tablet by wet granulation method. Accumulative in vitro dissolution rate of prepared tablets within 60 min were determined by UV spectrophotometry at 300 nm（using 0.2% tween as medium,paddle method）. Using original tablet as reference preparation,the similarity factor（f2）method was used to compare the similarity of dissolution behavior between 5 prepared tablets and original tablet. RESULTS：d（0.9）of powder A,B,C,D,E were 69.181,40.778,24.805,12.611,3.083 μm,respectively. The corresponding f2 were 27.77,36.79,50.06,67.68,79.99. CONCLUSIONS：The particle size of ticagrelor crude drug is much smaller,and the dissolution behavior of prepared tablet is closer to that of original tablet.The in vitro dissolution rate of Ticagrelor tablets is improved remarkably by micronization technology. In order to produce Ticagrelor tablets with the same bioavailability as original tablet,particle size of ticagrelor crude drug powder should be controlled with d（0.9）≤20 μm.