Application of Quality by Design Approach on the Development of Dobutamine Hydrochloride Injection
Objective Based on the concept of quality by design(QbD),to establish the quality target product profile(QTPP)of generic dobutamine hydrochloride injection,determine the critical quality attributes(CQA)of the target product,develop the con-trol strategy of pH value of the liquid medicine,and optimize the filling process to control the residual oxygen in the top space of the self-developed product.Methods The pH values of the solution were 2.0,2.5,3.3,4.0 and 5.5.Stress testing was conducted to further explore the effect of pH value of different liquid on the quality of the preparation.With filling speed,nitrogen flow rate be-fore and after filling,nitrogen flow rate before and during plugging as independent variables,and the measured residual oxygen as de-pendent variable,a partial factor test of 1/2 of 3 central points was performed and the nitrogen filling process was optimized.Results In the range of pH value 2.5-5.5,the properties of each sample,the clarity and color of the solution,the total impurity and each single impurity did not change,and the quality of the sample was stable.The best space of nitrogen filling parameters and filling speed of filling line 40%-67%were determined.Conclusion In this study,the pH value control range and the optimal nitrogen filling process parameters of generic dobutamine hydrochloride injection were determined,which were reasonable and feasible,and could better control product quality.
dobutamine hydrochloride injectionquality by designprescription technologyinjection
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