Preliminary Consistency Evaluation Of Mosapride Citrate Tablets

Objective:The preliminary consistency evaluation of Mosapride Citrate tablets was conducted between the domestically marketed generic drugs and the original drugs.The quality consistency between the generic drugs and the original drugs was improved through process improvement and optimization.Methods:HPLC method was used to determine relative substances of active pharmaceutical ingredient and tablets of Mosapride Citrate.Content homogeneity of Mosapride Citrate was determined using UV method.Paddle and HPLC methods were used to determine the dissolution rate of Mosapride Citrate tablets and evaluate the dissolution similarity between generic drugs and original drugs.Proteins in preprocessed blood samples were precipitated by acetonitrile.HPLC-MS/MS method was used to determine the blood drug concentration.DAS2.0 software was used to fit the drug-time curve.The statistical method was used to evaluate the bioequivalence.Results:1.The system applicability,specificity and precision of the relevant material detection methods were satisfied.The linearity of Mosapride Citrate in the range of 0.502μg/m L to 5.020 μg/m L was well.The relative substances of Mosapride Citrate active ingredient produced by M and N pharmaceutical factories met the requirements,while that of tablets produced by the domestic B factory exceeded the limit.2.The determination results of the tablets showed that all the percentage of labeled amount were within the range and met the requirements.3.The dissolution detection method had good system suitability and specificity.The solution was stable within 24 h(RSD = 0.44%).The precision was 0.05% and the recovery rat was 100.9%(RSD was 0.4%),which met the requirements.The linearity was good of Mosapride Citrate in the range of 0.28034 μg/m L to 16.82035 μg/m L.The limit of quantification was about 27.5 ng and the filter membrane was adsorbed of Mosapride Citrate(RSD > 2%).The dissolution rates of generic drugs manufacted by domestic A,B,and C plants were not similar to the original drugs(f2 factors were all less than 50).Some generic drugs had poor dissolution in vitro and needed to be improved.4.After adjusting the degree of micronization of raw materials,tablet hardness,coating composition and other processes,the process of the generic drugs pharmaceutical process at the domestic A factory were optimizated as follow: API particle size was 750mesh;the higher the tablet hardness,the higher the dissolution;the material of coating was water soluble.The dissolution curves in vitro of modified generic drugs were similar to the original drugs.5.HPLC-MS/MS method was established to determine the concentration of mosapride in rat plasma.The sensitivity and selectivity were high.The standard curve Y =0.0239 X + 0.0854,r = 0.9990,and mosapride had a good linearity in the range of 0.1ng/m L~100 ng/m L.Precision,accuracy and stability were good.The recovery was 79.97%to 81.29%.The minimum limit of quantitation was 0.05 ng/m L.The retention time of mosapride and internal standard were 3.5 min and 4.1 min,respectively.The main pharmacokinetic parameters of the generic drugs 1,generic drugs 2 and original drugs were Cmax: 34.84 ± 23.87 μg/L,0.14 ± 8.58 μg/L,33.87 ± 15.28 μg/L;Tmax: 0.32 ± 0.33 h,0.18 ± 0.03 h,0.181 ± 0.04;AUC0-τ: 80.47 ± 13.55 μg/L × h,51.34 ± 10.43 μg/L × h,51.79± 9.27 μg/L × h;AUC0-∞: 146.84 ± 44.23 μg/L × h,62.98 ± 19.14 μg/L × h,64.88 ± 15.31μg/L × h.Conclusion:Determination methods of related substances detection,content determination and dissolution rate in vitro were established,and the determination of blood concentration in vivo and pharmacokinetics for Mosapride Citrate tablets were also studied in this study.The multiple dissolution curves in vitro of generic drugs which were produced after optimizing the process and original drugs were similar,and there was no difference in the main pharmacokinetic parameters.