Preparation And Quality Control Of Dimethyl Fumarate Enteric-coated Capsules

Multiple-sclerosis(MS)is a complex,disabling chronic neurological disease.The main clinical symptoms are numbness of the limbs,optic neuritis caused by decreased vision,difficultly walking,sexual dysfunction and extreme fatigue,which are mainly observed in young adults.There is no independently researched and developed drug for Multiple-sclerosis(MS)in the market at present,the permission of Bai Jian Ai Di's Tecfidera(?)capsule for the treatment of recurrent Multiple-sclerosis was allowed by FDA in 2013.Tecfidera has a better effect on MS relapse and less serious security risks or monitoring requirements as well as acceptable tolerance comparing with other intravenous drugs.Tecfidera enteric capsule is only putted into American,Canada and German market.This study establish a simple and reliable liquid chromatography(LC)method for an effective estimation of dimethyl fumarate enteric-coated capsules,related substance as well as it's release in vitro.The established method is proved to be of strong specificity.good repeatability and high accuracy by systematic study on methodology.Tecfidera enteric capsule containing with dimethyl fumarate is a gelatin capsule with enteric coat coated mini-tablets that is filled into capsule after coating.In this study,microcrystalline cellulose is used as filler,croscarmellose sodium as disintegrant.magnesium stearate,talc as lubricant,silica as glidant,the micro table is prepared by lengthwise pressed powder.The single factor test can be adopted in selection of excipient quantity.optimal prescription of preparation can be determined by prescription selection.The enteric coating preparation use methacrylic acid copolymer type A.methacrylic acid copolymer dispersion as coating material,talc as coating anti-blocking agent.triethyl citrate as coating plasticize.Preparation of dimethyl fumarate enteric-coated capsules is finished with adding the entric micro table into capsule.The optimal preparation,key steps and parameters of dimethyl fumarate enteric-coated capsules are determined by prescription selection and process researches.A comparative study of total quality between own products and the original research agent is conducted in this study to estimate the release curve of own products and the original research agent in pH 6.8 phosphate buffer,pH 6.0 phosphate buffer,pH 4.5 acetate buffer and water.The release behaviors of own products is consistent with original research agent.In the study,influencing factors test,accelerated test and long-term test indicate no significant difference in indicators compared with that in 0 month,and the indicators meet the requirements.