The Quality Research Of Anastrozole And Anastrozole Tablets

This subject for the national drug quality standards was issued by the State Pharmacopoeia Committee of China.The objective of this study was to improve the quality standards of anastrozole drug substance and its tablets by the application of modern analysis technology.It provides a scientific basis for increasing and revising the quality control project of Chinese Pharmacopoeia.The first part of the thesis develops a new gradient HPLC method for the determination of related substances of anastrozole drug substance and its tablets.The inspection methods of related substances in domestic and foreign standards were compared.Meanwhile,the study investigates and selects the optimum conditions of mobile phase,gradient elution program and measurement wavelength,and establishes the methodology validation.The method are specific and sensitive.The second part destablishes a capillary gas chromatographic methodfor determination of 11 residual solvents in anastrozole drug substance.The experimental conditions,such as the sampling method,the column temperature and the solution medium,were studied and the methodology validation was established.The method is proved to be accurate and reliable.Meanwhile,the residual solvent in several samples were confirmed by GC-MS.The third part researches the dissolution test method of anastrozole tablets.It refers to the import registration standard,then The small cup method in current standards to paddle method,the speed from 100 rpm to50 rpm.The anastrozole tablets dissolution test method become more scientific and reasonable.The fourth part evaluates the similarity of the dissolution curve of domestic and foreign anastrozole tablets.It studies vitro dissolution behavior of the domestic anastrozole tablets in four different dissolution media,the similarity of the dissolution curve of the foreign original tablets was compared.The dissolution curve of the products of 3enterprises in China is similar to the foreign original tablets.The fifth part through the simulation of drug absorption and release behavior of GastroPlus,on the basis of physicochemical properties and reported the pharmacokinetic parameters of anastrozole,combined with in vitro dissolution experiments results,established in vivo correlation model,the prediction of anastrozole tablets oral pharmacokinetic parameters andevaluate its bioequivalence.