In vivo and in vitro Evaluation of Esomeprazole Magnesium Delayed-Release Oral Suspension
Objective:To explore dissolution profile characterization methods for prescription screening in scale-up production,to screen appropriate batches of formulations for in vivo bioequivalence studies,and to reduce the risk of in vivo bioequivalence testing.Methods:The dissolution curves of different batches of formulations(with different weight gain in the enteric layer)are characterized by dissolution instrument paddle method and flow-through cell method,and suitable formulations are selected for fasting state and fed state bioequivalence(BE)studies.Results:There is a small difference in dissolution between formulation A with 30%weight gain of the enteric coating layer and formulation B with 32%weight gain of the enteric coating layer in the 1.0 mol/L HCl-pH 6.8 phosphate buffer solution.In the pH 4.5-pH 6.8 phosphate buffer solution,the dissolution curves of formulation A and the reference listed drug are better fitted.As a result for fasted and fed state BE study,the geometric mean ratios of Cmax,AUC0-t,AUC0-∞,and 90%confidence interval of esomeprazole are falling within the equivalent range of 80.00%to 125.00%.Conclusion:The formulation A with a 30%weight gain in the enteric-coated layer is bioequivalent to the reference formulation,and the dissolution instrument paddle method combined with the flow-through cell method can improve the efficiency of drug research and development.
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