他达拉非片的制备及人体生物等效性研究  

Study on Preparation and Bioequivalence of Tadalafil Tablets

作　　者：王征 黄小宏 钟雅妮 WANG Zheng;HUANG Xiaohong;ZHONG Yani(Zhuhai United Laboratories Co.,Ltd.,Zhongshan,Guangdong 528400,China)

机构地区：[1]珠海联邦制药股份有限公司,广东中山528400

出　　处：《今日药学》2023年第4期268-272,310,共6页Pharmacy Today

摘　　要：目的以Cialis(20 mg)为参比制剂进行他达拉非片处方工艺开发,并研究二者的生物等效性。方法参照Cialis处方组成,采用经微粉化处理的他达拉非原料制备片剂,以溶出曲线的相似性作为评价指标,筛选处方中黏合剂浓度、片芯硬度、湿法制粒参数和原料前处理方式,最终通过生物等效性研究确定处方工艺。结果以Cialis处方组成为基础,选择黏合剂浓度8%、片芯硬度6~9 kg、湿法制粒3~4 min、原料气流粉碎,制得片剂与Cialis在不同溶出介质中均相似。口服给药后,人体药动学参数为:自制品C_(max)为(272.78±42.22)ng·mL^(-1),T_(max)为(2.10±0.57)h,Cialis的C_(max)为(302.38±63.20)ng·mL^(-1),Tmax为(2.70±0.89)h;自制品与Cialis的C_(max)、AUC_(0-t)和AUC_(0-∞)的90%置信区间均落在80%~125%范围内。结论采用经确认的处方工艺制备他达拉非片,可实现与Cialis体外溶出一致和体内生物等效。OBJECTIVE To selected Cialis(20 mg)as the reference to develop the prescription of tadalafil tablets,and to study their bioequivalence.METHODS According to the prescription of Cialis,the micronized tadalafil was used to prepare tablets,and the similarity of dissolution curve was used as the evaluation index.The binder concentration,tablet hardness,wet granulation parameters,and pretreatment of raw material in the prescription were screened,and finally the prescription process was determined by bioequivalence study.RESULTS Based on the prescription of Cialis,the binder concentration 8%,tablet hardness 6⁃9 kg,wet granulation for 3-4 min and raw material jet⁃milling were selected.The prepared tablets were similar to Cialis in different dissolution media.After oral administration,the pharmacokinetic parameters in human body were as follows:C_(max)was(272.78±42.22)ng·mL^(-1)and T_(max)of self⁃made product was(2.10±0.57)h.Cmax and Tmax of Cialis were(302.38±63.20)ng·mL^(-1)and(2.70±0.89)h.The 90%confidence intervals of C_(max),AUC_(0-t)and AUC_(0-∞)between self⁃made products and Cialis all fell in the range of 80%~125%.CONCLUSION Tadalafil tablets are prepared by the confirmed prescription process,which can be consistent with the dissolution in vitro and bioequivalent in vivo of Cialis.

关 键 词：他达拉非 处方工艺 体外溶出 生物等效 

分 类 号：TQ460.6[化学工程—制药化工] R944.4[医药卫生—药剂学]