Abstract
Coadministration of antihypertensive and antidiabetic drugs is quite common, as both of these medical conditions often occur together. In the present work, a simple and accurate RP-HPLC chromatographic method was developed for the simultaneous determination of the antihypertensive drug carvedilol (CRV) and the hypoglycemic agent glimepiride (GMP) or glibenclamide (GBD). This study was carried out using an isocratic reversed phase high-performance liquid chromatographic method using a C18 column with ultraviolet detection at 220 nm. The system was operated at flow rate of 1 mL/ min using a mobile phase consisting of 70:30 v/v methanol: 0.2M phosphate buffer (pH 3.5) and column temperature adjusted to 30 oC. The developed RP-HPLC method has been successfully applied for the estimation of carvedilol and glimepiride or glibenclamide in their binary combination laboratory prepared tablets with assay percent range 99.49- 99.95 % and relative standard deviation less than 1% indicating satisfactory accuracy of the method. The method was validated according to the ICH guidelines; the linearity range is 2-75 μg/mL for CRV and 5-300 μg/mL for each GMP and GBD; precision, accuracy, robustness, ruggedness, specificity, LOD and LOQ were also evaluated. The RP-HPLC method was also applied in investigating the possible in vitro drug interactions of carvedilol and glimepiride or glibenclamide. This study was carried out at 37oC in simulated gastric juice pH 1 or simulated blood pH (pH 7.4). It was observed that after interaction of carvedilol with glimperide or glibenclamide, the % availability values of the two antidiabetics were decreased, by about 10 and 20% for glibenclamide and glimepiride, respectively. In vivo pharmacological studies were recommended, which can help with the in vitro study in the improvement of clinical efficacy of the coadministered drugs. The developed RP-HPLC method is rapid, sensitive and accurate and can be applied in quality control laboratories for routine determination of carvedilol, glimepiride or glibenclamide in their binary mixtures, and also it can be applied to samples of in vivo subjects.