Different resolution techniques for management of overlapped spectra: Application for the determination of novel co-formulated hypoglycemic drugs in their combined pharmaceutical dosage form

Abstract

To maintain intensive glucose control early in the type II diabetes mellitus process, novel combinations of canagliflozin/metformin (CAG/MEF) and empagliflozin/linagliptin (EMG/LIG) offer particular treatment benefits. In this study, sensitive and precise spectrophotometric methods were developed for the determination of such hypoglycemic drug combinations in bulk powder and in pharmaceutical dosage form without prior separation. The first method was ratio difference coupled with modified isosbestic point technique where the amplitude difference between 239 and 291 nm on the ratio spectrum of CAG obtained using 4 μg/ml of MEF as divisor was used for determination of CAG. On the other hand, MEF was estimated using a modified isosbestic spectrophotometric method, where the total concentration of CAG and MEF in mixture could be calculated at 250 nm (isosbestic point) after multiplication by a correction factor. Then concentration of MEF could be calculated by subtraction. The second method was ratio subtraction coupled with extended ratio subtraction, where EMG was determined at 225 nm by subtraction of plateau values from the ratio spectrum followed by multiplication with the spectrum of 6.5 μg/ml of LIG (divisor). Then, an extension of the normal ratio subtraction method was performed in order to determine LIG at 226 nm. Linearity was obtained over 5–30, 2.5–16, 2.5–16 and 1.25–8 μg/ml for CAG, MEF, EMG and LIG, respectively. The developed methods were successfully applied for the determination of studied drugs in tablets. Validation parameters were found to be within acceptance limits, thus confirming methods accuracy and selectivity. The obtained results were statistically compared with the reported one showing no significant difference in terms of accuracy and precision. The methods could be applied for routine analysis of the cited drugs in quality control laboratories.