The Studies On The BCS And Key Technology For Quality Control Of Estazolam

Estazolam belongs to benzodiazepines sedative-hypnotics. After oral administration,Estazolam tablets rapidly absorbed through the gastrointestinal tract, cross theblood-brain barrier, bind the brain GAGBA receptor, and activate the GAGBAreceptors.It promote GAGB-induced Cl-influx, and hyperpolarizing the cells thus play a role ofrestraining the excitement, sedative and hypnotic.Estazolam used for many years as a reliable efficacy and safe sedative hypnotics. Itis of widely used in clinical practice, and was listed as China’s basic medicine. Althoughapplied for many years in clinic, it is lack of a comprehensive study of its quality. Withthe development of generic drug quality assessment project in foreign drugadministration departments, our country gradually pay attention to the quality of generics,and has already begun on the quality evaluation of generics.We have studied the quality consistency of generics estazolam. Tests include thefollowing three parts:1The BCS of estazolam has been discussed.Recently, FDA, WHO and EMA have beencarried out exemption of bioequivalency for generics drugs and prescription changebased on Biopharmaceutics Classification System. The application of BCS has beengradually accepted. In order to further study the BCS of estazolam. Caco-2cell model isadopted to research the permeability of estazolam and possible factors affecting transportmechanism. According to the solubility and in vitro permeability, estazolam is classifiedacross BCS.2Modified the existing methods of dissolution test from small vessels to standard vessels.Existing UV spectrophotometric detection methods is improved to a more specificityHPLC method, and dissolution medium is well selected. Classify the existing generics bytested both generics and original drugs using modified dissolution methods andcomparing the similarity of f2factor and Weibull curve.3In order to further control of estazolam quality, we conducted in-depth research onestazolam’s related substances. Researched estazolam stability under different conditions,and separated photodecomposition products by TLC. Its accurate molecular weight andstructure is determined by LC-MS.In these experiments, we evaluated the quality consistency of estazolam tablets, improved part of the testing standard, and provided the basis of standards re-establish.