Formulation Process And Quality Research Of Roflumilast Tablets

Objective:Roflumilast Tablets,which the active ingredient of roflumilast,is a kind of new selective PDE-4 inhibitor,that is clinically mainly used to treat Chronic Obstructive Pulmonary Disease(COPD),it has best safety and tolerability,so it would be the first choice against COPD.Rofluskate Tablets,trade name Daxas,Nycomed was first approved by the European Union in July 2010.This is the first new type of COPD treatment approved by the European Union in recent years.Roflumizol tablets were approved for listing by the FDA in March 2011.However,the product isn't available in China,and with more and moreCOPD patients now,there is a huge potential market in China.In order to provide the foundation for preclinical and clinical research of Roflumilast Tablets,the author have studied on the synthesis of raw materials,the formulation process and the draft of quality standard.Under the draft's guidance,we can get the same or even better quality new product.Methods:(1)Studies on the formulation process:Thissubject based on the patent of reference product and instructionsof Roflumilast Tablets(Daxas),the author observes the main index of the tablet,eg,appearance,hardness,disintegration time and stripping phenomenon,and then determines a better formulation and preparation procedure on the basis of test results.(2)Quality research:Referring to the pharmacopoeias,review principle,the relevant requirements of the international CTD and references,the author studied the quality of Roflumilast Tablets,including characteristics,the design of identification methods of UV and HPLC and the establishing of methods of inspection item about dissolution rate,content uniformity,and the building of measuring methods,and then validated a methodology to the dissolution rate,related substances and content determination,including specificity,linear,instrument precision,stability and recovery rate.On the basis of that,the quality standard draft was established.The system was used to test two bath of products from small scale experiment,three baths of products from pilot scale experiment and some commercially available products.(3)Stability:On the foundation of the quality standard in this study,according to the domestic and foreign review principle,the author have studied the stability of Roflumilast Tablets,including stress test,accelerated test and long-run test.Results:(1)Studies on the formulation process:Taking appearance properties,weight differential,hardness,disintegration time and angle of repose,friability,dissolution rate and content determination into consideration,studying on the formulation process,the results show that recipe 10 is the best,that is Roflumilast(0.5mg),lactose(130mg),starch(100mg),,Pregelatinized Hydroxypropyl Starch(30mg),adhesive(Povidone K30:3mg),lubricant(magnesium stearate:1.3mg).According to the appearance properties,dissolution rate and content determination,the formulation process was established,that is dissolvingRoflumilast the binder,the mesh was 20 mesh,the whole grain sieve of 26 mesh,moisture content of pellet<3%,total mixed time of 20 minutes,tablet hardness was less than4.0kg,oating weight in the range of 1%to 3%.(2)Establish the quality standard:Established a detection method for some key projects,for example,the dissolution rate,related substances and content determination.Completed a whole quality standard draft of Roflumilast Tablets according to the comparison and validation of all the test parameters.The quality standard draft has through the investigation of methodology.(3)Stability:The good results of stress test,accelerated test and long-run test to the one bath of products from small scale experiment,three baths of products from pilot scale experiment show that the product has stable quality.Conclusion:This study has developed Roflumilast Tablets successfully,which is similar to the Reference Listed Drug's quality,more stable and effective.At the same time,the quality standards for Roflumilast Tablets have been established.The quality standards for this study have ensured the stability of product quality and effectively controlled the intra-batch and inter-batch differences.