Study On Quality Standard And Stability Of Roflumilast Tablets

Chronic obstructive pulmonary disease,abbreviated to COPD,it is a fatal lung disease which could cause serious disability.It becomes one of the leading causes of illness and death in the world.The present research shows that chronic airway inflammation is involved in the occurrence and development of COPD,and selective inhibitors of phosphodiesterase-4(phosphodiesterase4 inhibitor PDE-4)has a broad anti-inflammatory effect,for the treatment of acute exacerbation in adults with frequent severe COPD.Different from other drugs,roflumilast tablets is the world's first allowed for clinical treatment and selective inhibitor of PDE-4 oral treatment of COPD only.Currently roflumilast is on market only in the United States and the European Union,while no domestic imports to China.So roflumilast belongs to the third category of new drugs in china.In order to ensure the safety and effectiveness of clinical use of drugs,we here made a comprehensive study on the quality of the roflumilast tablet.First of all,the character,identification and examination of roflumilast tablet were established.The related substances,dissolution degree determination and content are as the main studied objects.The methodology validation including method specificity,limit of detection and quantification,linear range,precision,accuracy,stability and durability were detected respectively.The examination of related substances was developed in reversed-phase liquid chromatography with gradient elution conditions and using own control method without calibration factor calculation of complex quality method were explored.Determination of content was used isocratic elution method and optimized based on the method of related substances detection.Secondly,we used the paddle method for the development and validation of roflumilast tablets dissolution according to the China Pharmacopoeia 2015 edition.Aimed at the difficults of small size(only 0.5 mg/table)for roflumilast tablets and the main drug insoluble problems,we studied the composition of the dissolution medium and optimized the treatment methods of the dissolution solution.Through adding SDS as the surfactant to the dissolution medium and centrifugation treatment of the solution,we explored an appropriated method to meet the requirements of the determination of dissolution.And the methodology validation of dissolution determination was also studied.We found that the particle size of raw material has a great influence on the dissolution rate.In order to ensure the quality of the product,the D90 particle size of the raw material should be controlled to less than 15 ?m.Finally,the stability studies of roflumilast tablets were carried on at different conditions including high temperature,high humidity,light and other long term and accelerated test conditions.The results of these experiments showed that the appropriate storage conditions of roflumilast tablets should be sealed at room temperature.In summary,through the research on the quality of roflumilast tablets,we established the quality standard draft of roflumilast tablets.The developed method has important significance on the quality of roflumilast tablet control.This study provides an important guarantee for the quality control of roflumilast domestic tablets.