Objective  To determine the dissolution curves and related substances of domestically produced trimetazidine hydrochloride tablets after process improvement and the original formulation by HPLC method, and evaluate the consistency of domestically produced formulations after process improvement.

Methods  In the dissolution determination, a Phenomenex Gemini (150  mm×4.6  mm, 5 μm) chromatographic column was used, the mobile phase was [0.287% anhydrous sodium heptanesulfonate methanol (643 ∶ 357)]-methanol (70 ∶ 30), the detection wavelength was 231 nm, the flow rate was 1.0 mL/min, the column temperature was 40℃, and the injection volume was 20 μL. The dissolution media were pH 1.2, pH 4.0, pH 6.8 buffer salt solution, and water. The paddle method was used with a rotation speed of 50 r/min and a dissolution volume of 900 mL. The dissolution curves of domestically produced trimetazidine hydrochloride tablets after process improvement and the original formulation in the four dissolution media were investigated. In the determination of relevant substances, gradient elution was used with a detection wavelength of 240 nm, and the other chromatographic conditions were the same as those used for dissolution determination.

Results  In the established dissolution determination method, there was a good linear relationship between the peak area and the concentration range of 4.58-45.80 μg/mL of trimetazidine hydrochloride (r=0.999  9), with an average recovery rate of 99.7% (RSD=0.71%, n=9). The established substance detection method could effectively separate trimetazidine hydrochloride from 9 known impurities, each impurity and trimetazidine showed a good linear relationship with peak area within a certain concentration range (r>0.999 0), the correction factors were 0.99-1.07, and the average recovery rate was 98.0%-100.9% (RSD=0.33%-0.96%, n=9). The dissolution curve of domestically produced trimetazidine hydrochloride tablets after process improvement was consistent with that of the original formulation, but there were significant differences in the number and content of impurities detected compared to the original formulation.

Consultion  The domestically produced trimetazidine hydrochloride tablets after process improvement may achieve bioequivalence with the original formulation, but the quality is not equivalent. Further process improvement is needed to achieve the goal of the dissolution curve and related substances being consistent with the original formulation.

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