In Vitro And In Vivo Data Analysis Of Atorvastation Calcium Tablets

Objective:The in vitro and in vivo correlation of atorvastatin calcium tablets was studied by comparing the in vitro dissolution behavior and in vivo bioequivalence of the test preparation of atorvastatin calcium tablets in a pharmaceutical company with the original preparation.By analyzing the blood concentration data of 64 subjects in the fasting test and 64 subjects in the postprandial test,the number of bioequivalence test cases and the influence of age,sex and BMI on the atorvastatin calcium Cmax value were investigated.Early screening or rational adjustment of preparations and processes,and establish a more discriminatory dissolution profile and provide a reference for developing more rational clinical trial protocols for bioequivalence studies.Methods:The in vitro and in vivo correlation evaluation methods were determined through literature research,and the similarity of the six dissolution profiles of atorvastatin calcium tablets produced by a certain pharmaceutical factory with the original preparation agent was compared,and the cumulative dissolution in vitro was calculated.The in vivo bioequivalence test was performed to calculate the in vivo absorption fraction at the corresponding time point.The cumulative absorption percentage?F?in the body and the in vitro dissolution?Q?of the corresponding time point were linearly regressed,and the most discriminating dissolution curve and its in vitro and in vivo correlation were determined according to the correlation coefficient r.The plasma concentration data of 64 subjects in the fasting test and 64 subjects in the postprandial test were randomly divided into several groups,and the 90%confidence of C_max,AUC_0-t-t and AUC_0-?in each group was calculated by DASS 3.2.8 software.The interval was evaluated for bioequivalence of the test preparation and the reference preparation.Deeply excavate the setting of the number of cases in bioequivalence trials and the changes of pharmacokinetic parameters under different parameters.Results:The dissolution profile of the atorvastatin calcium tablet test preparation and the reference preparation in 6 different dissolution media in vitro is consistent.;the fasting and postprandial bioequivalence test in vivo,Cmax,AUC0-t,AUC0-?geometry of the test preparation the statistical results of the 90%confidence interval of the mean ratio are within the acceptable range of 80.00%¹25.00%,and the test preparation is bioequivalent to the reference preparation.The cumulative absorption percentage?F?and the in vitro dissolution?Q?linear regression coefficient r of the test preparation in0.01 mol/L hydrochloric acid solution was the highest,P<0.05,statistically relevant.The 90%confidence interval results of the randomized groups Cmax,AUC0-t,AUC0-?,and the sample size statistical software calculations all indicated that 34 subjects in the batch test of the test preparation in the fasting test,24 subjects after the meal test can be used with the reference Equivalent to the formulation.The Cmax value of women taking atorvastatin calcium tablets is generally about 30%higher than that of men.Conclusion:The dissolution of atorvastatin calcium tablets in vitro is pH-dependent.Correlation analysis with in vivo data shows that the dissolution behavior at pH 2.0 is the most discriminating.However,it has not been found that there is a good in vitro and in vivo correlation between atorvastatin calcium tablets.Although atorvastatin calcium tablets are highly variable drugs in the body,if the preparation is highly consistent with the original research,pay attention to the instability of the original form and its metabolites and add appropriate stabilizers when conducting bioequivalence tests.Significantly reduce the number of cases in the bioequivalence trial.Gender also had a significant effect on the Cmax value of atorvastatin calcium tablets.