Research And Scale-Up Production Of Valsartan And Amlodipine Bi-laver Tablets

Hypertension can lead to heart disease,cerebrovascular disease,kidney disease and peripheral vascular disease,lead to stroke or myocardial infarction,and even lead to death.Effective control of blood pressure in patients is the key to reduce cardiovascular events.Blood pressure in patients usually controlled by multi-drug combination therapy clinically.Valsartan and amlodipine tablets is the world's first ARB/CBB compound preparations approved by the FDA,which can make 90%of the patients blood pressure under control.Valsartan and amlodipine tablets(Trade name:Exforge)is a compound antihypertensive agents developed by NOVARTIS,which is approved by FDA in June 2007,market in strengthes of 160/5 mg,160/10 mg,320/5 mg and 320/10 mg.After launched,the safety and effectiveness of Exforge was proven by doctors and patients,the global sales of Exforge is about $1.1 billion in 2015.Up to September 2016,FDA has approved 8 AND As but without any Chinese company.Zhejiang Huahai Pharmaceutical Co.,LTD.,a Chinese pilot internationalized enterprise,is vigorously developing AND As,valsartan and amlodipine tablets is one of the key projects.The main purpose of this research is to develop generic tablets of valsartan and amlodipine tablets,which is bioequivalent with the brand,benefit the patients and create huge economic benefits for the company.The main results were as follows:(1)On the basis of pilot-BE study,an IVIVC dissolution method(pH1.0 hydrochloride 1000 mL,paddle 75 rpm)is developed;(2)By single factor investigation or factorial experiment design,the formulation and process of generic tablets is developed under the guidance of IVIVC dissolution method,the final products have good stability,and the dissolution profiles matched with the brands in different pH mediums.(3)The scale-up strategy of the products is determined on the basis of process development,theoretical knowledge and practical experiences.Three consecutive submission batches are produced according to this strategy,proved robust process and good stability,the product conforms to the requirement of predetermined quality standards,and the dissolution profiles matched with the brands in different pH mediums.Samples from the second batch of 320/10 mg strength is selected for bioequivalence study,the results can be expected in early 2017.