DISSOLUTION KINETICS STUDIES OF CLOPIDOGREL FROM SELECTED MULTISOURCE COATED TABLETS WITH APPLICATION OF CAPILLARY...

Resistance to an anti-platelet agent clopidogrel (CLP) and the growing number of products with the drug cause the need for comparison of their quality to assure patients safe and effective treatment. Therefore, the aim of the study was to compare in vitro dissolution kinetics of CLP immediate-release tablets, commonly used in anti-platelet therapy in Poland. For analysis of CLP in samples obtained from dissolution test a capillary zone electrophoresis (CZE) method was elaborated and validated. Separation of CLP and ticlopidine, used as an internal standard, was performed in silica capillary filled with phosphate buffer of pH 2.5, at the applied voltage of 20 kV. The CZE method fulfilled the validation requirements for determination of drugs in pharmaceutical matrices and was successfully applied for analysis of CLP dissolved from the tablets. Dissolution profiles were prepared for each product and mean dose fractions of CLP dissolved from tablets at 30 min were calculated. Kinetic parameters of the CLP dissolution from the studied products were compared. Analysis of variance (ANOVA) did not reveal differences between CLP fractions dissolved at 30 min time point from the tested drug products. However, ANOVA with Tukey multiple comparison test revealed significant differences in first-order dissolution rate constants and t₀.₅ values (times at which 50% of drug is dissolved) of CLP among tested tablets. It was concluded that the studied CLP products met the acceptance criteria regarding dissolution test but differed with each other in dissolution kinetics.