Consistency Evaluation Of Felodipine Tablets Based On QbD

Felodipine is a second-generation dihydropyridine calcium channel blocker(CCB)and it is specifically bound to calcium channels to inhibit calcium influx to bring about myocardial contractility decrease,heart rate reduction,blood vessel relaxation and fall of blood pressure.In the WHO,European and Chinese guidelines for hypertension,all anti-hypertensive drugs commonly prescribed include CBB,which is widely used at home and abroad.This is a study on consistency evaluation based on the concept of QbD with felodipine tablets(5mg)produced by AstraZeneca,a Japanese plant,used as reference preparation.In the preformulation study,QTPP and CQA were formulated with initial risk assessment of prescription variables by investigating the properties of reference preparation,APIs,excipients and packaging materials;in the prescription study,based on the study of the prescription dosage and treatment method of APIs,diluents,binders and lubricants according to the risk assessment,the laboratory trial prescription of felodipine tablets was determined,whose similarity factor f2 with the reference preparation in pH6.8 dissolved medium was 81.2,and the laboratory finding showed a reduction in the risk of the prescription variables to the finished product;in the process study,the process steps of API comminution,granulation,drying,mixing,tablet pressing,coating and packaging were investigated according to the initial risk assessment of the process variables and the production process of the product was determined,which reduced the risk of process variables to the finished product.DOE factor design was performed by Minitab in the prescription and process study,and the factors were scientifically studied.According to the pre BE study of 12 patients with fasting and fed administration of the drug vs the reference preparation felodipine tablets(5mg)produced by AstraZeneca in Japan,the 90%confidence limits of fasting AUC0-36 h,AUC0-? and Cmax were 77.47%?106.80%,80.92%?106.77%and 88.31%?119.26%respectively,and the 90%confidence limits of fed AUC0-36h,AUC0-? and Cmax were 95.47%?116.34%,92.20%?112.62%and 80.48%?119.18%respectively.The 90%confidence limit of fasting AUC0-36h of the test product did not fall within the range of 80.00%?125.00%of the reference preparation,indicating the two were not bioequivalent;those of fed AUC and Cmax fell within the range of 80.00%?125.00%,indicating the two were bioequivalent.The results of pre-BE will provide a reference for the follow-up study of the product.