Study On In Vitro Release Method And Impurities Of Felodipine Sustained-release Tablets

Objective:1.Established the release measurement method of felodipine sustained-release tablets bythe reciprocating cylinder dissolution measuring device,and compared and analyzed the related influencing factors that affect this method;2.According to the reciprocating cylinder dissolution The determination method establishes multiple dissolution curves of reference formulations and imitation formulations of felodipine tablets in different dissolution media and conducts consistency evaluation;3.A preliminary study of the impurities of felodipine and the impurities A and B by liquid-mass spectrometry technology,the structure and formation path of C are analyzed,and the impurity spectra of felodipine tablets of different manufacturers are compared.Methods:1.Compared the different content determination methods of felodipine sustained-release tablets,and select HPLC chromatography to determine the content of felodipine and related methodological verification.2.Investigate the equilibrium solubility of felodipine in different types and concentrations of surfactants,and determine the dissolution medium and volume involved in the research of this topic;meanwhile,it affects the reciprocating frequency and screen size in the reciprocating cylinder dissolution test The relevant influencing factors of dissolution were compared and analyzed,and the determination conditions of the in vitro release method of felodipine sustained-release tablets for reciprocating cartridge dissolution were established.3.The research was determined by reciprocating cylinder apparatus with bath temperature 37℃and dip rate 10 dpm.The dissolution profiles was studied in different p H（1st row:p H1.2,2nd row:p H6.5）dissolution which respectively containing 0.3%Tween 80,0.1%CTAB,and 0.2%SDS.The similarity of generic and reference formulation was evaluated by?₂factor method.4.Using HPLC method to study the impurities of felodipine sustained-release tablets,and to carry out the methodology and related stability investigation of the related substance determination methods.The UPLC-Q Exactive quadrupole-electrostatic field orbit trap high-resolution liquid-mass spectrometry technology was used to further determine and confirm the impurities of Felodipine.The impurity spectra of the comparison preparation and the imitation preparation were compared.Results:1.Determined the content of the selected reference preparation and imitation preparation,the content is be Tween 95%and 105%,which are in line with the regulations,and can be used to carry out dissolution method research.2.The concentration of the surfactant and the mesh number of the upper screen have a greater influence on the in vitro release of the reciprocating cylinder method,and the reciprocation frequency has little effect on the mesh number of the lower screen.3.Use the?₂similarity factor method to compare the similarity be Tween generic and reference preparations.Compared with reference formulation,the results indicated that:1)company A was not similar in three medium,2)company B was not similar in the medium containing SDS,3)company C was not similar in two medium which respectively containing Tween 80 and CTAB.4.The destruction test and accelerated test results show that the felodipine sustained-release tablets are prone to produce impurities under high temperature and high humidity conditions.Impurity A is a degradation impurity,and impurities B and C are process impurities.Conclusion:The reciprocating cylinder method with low-level dip rate established in this study,which has the advantages of simulating the gastrointestinal environment and achieving the same effect as the high-level speed of the paddle method,provides reference for the process improvement of generic drugs.The structure analysis and speculation of the formation mechanism of impurities A,B,and C in felodipine sustained-release tablets provide data for the research of this variety of impurities.