An eco-friendly strategy, using on-line monitoring and dilution coupled to a second-order chemometric method, for the construction of dissolution curves of combined pharmaceutical associations

Abstract

A simple, precise, economic and minimally operator-dependent method was developed under green analytical chemistry principles, for the simultaneous construction of the dissolution curves of a pharmaceutical association in short time and without employing organic solvents, allowing important savings of labor and resources. The carvedilol (CAR) and hydrochlorothiazide (HCT) combined formulation was employed as a model. The method (OD/UV-MCR) involves on-line sample dilution (OD) and UV detection of the analytes, coupled to multivariate curve resolution with alternating least squares (MCR-ALS). OD/UV-MCR proved to be robust and was successfully validated in accordance to ICH guidelines, fulfilling acceptance criteria for specificity (r2 of spectral correlation > 0.950), linearity [r > 0.999 (N = 25) in the ranges 1.00–31.1 mg l−1 and 0.51–15.2 mg l−1 for CAR and HCT, respectively] and precision (RSD < 2%). Accuracy was assessed by point-to-point comparison between the dissolution profiles furnished by the proposed method with those provided by HPLC analysis, evidencing the usefulness of this monitoring system. In addition, OD/UV-MCR was successfully employed for the comparative analysis of three lots of commercial formulations of the CAR–HCT pharmaceutical association, belonging to a couple of different brands, employing Moore and Flanner's f2 similarity indicator.