title: 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 (r(2) of spectral correlation>0.950), linearity [r>0.999 (N=25) in the ranges 1.00-31.1mg l(-1) and 0.51-15.2mg 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.
authors.affiliation: Pharmaceutical Analysis, Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Calvo
authors.affiliation: Pharmaceutical Analysis, Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina.
authors.forename: Rubén M
authors.initials: RM
authors.lastname: Maggio
authors.affiliation: Pharmaceutical Analysis, Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina. Electronic address: kaufman@iquir-conicet.gov.ar.
authors.forename: Teodoro S
authors.initials: TS
authors.lastname: Kaufman
mesh_terms: D002227:Carbazoles / Q000737:chemistry*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006852:Hydrochlorothiazide / Q000737:chemistry*; D007201:Indicator Dilution Techniques; D016018:Least-Squares Analysis; D009862:Online Systems; D011412:Propanolamines / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D006852:Hydrochlorothiazide; D000077261:Carvedilol
keywords: Green analytical chemistry; MCR-ALS; Simultaneous dissolution profiles