Studies On Quality And Prescription Process Of Obeticholic Acid Tables

Primary biliiary cholangitis,as a chronic cholestasis disease,affects living quality of the patients.Recently,it has been found that the etiology of primary biliiary cholangitis is associated with genetic factors,environment factors,immune factors and life style,however,the specific cause is still not clear.Nonalcoholic fatty liver disease,a clinical syndrome unrelated to excessive alcohol intake,is characterized by diffuse fatty degeneration of liver cells and fat accumulation.Ursodeoxycholic acid is the only therapeutic drug approved by FDA,but it is universally effective,and there are one third of patients with an inadequate response.Farnesoid X receptor(FXR)is a member of the nuclear hormone receptor superfamily of ligandactivated transcription factors.Bile acids are FXR physiological ligand.As a metabolic regulator,FXR plays key roles in regulating metabolism of bile acids,lipids and glucose.Obeticholic acid is a new derivation of chenodeoxycholic that is the primary bile acid,and is also a farnesoid X receptor agonist.Obeticholic acid is listed in USA as a new drug,developed by Intercept Pharmaceuticals,for treatment primary biliiary cholangitis.The key of the study is that whether the dissolution behavior of obeticholic acid tablets we prepared are similar to original product,and whether the tablets can be producted industrially.Physicochemical property of obeticholic acid was studied in this topic,which laid the foundation for the obeticholic acid tablets.The high performance liquid chromatography methods for the dissolution test,the content uniformity and content determination to control the quality of obeticholic acid tablets were established.The formulation and process were screened and compared with the original product,and the final prescription was determined.This study found that the methods addition of disintegrants was the key process parameters.The coated tablets were adopted to ensure the quality of obeticholic acid tablets.According to the prescription and process parameters of the pilot production,three batches of products were produced.Results of the affected factor test showed that the detection results of dissolution,related substances,content and trait were similar to original product,indicating that the pharmaceutics had good stability and the process was easy to operate and suitable for industrial production.