A comprehensive strategy in the development of a cyclodextrin-modified microemulsion electrokinetic chromatographic method for the assay of diclofenac and its impurities: Mixture-process variable experiments and quality by design.
A comprehensive strategy involving the use of mixture-process variable (MPV) approach and Quality by Design principles has been applied in the development of a capillary electrophoresis method for the simultaneous determination of the anti-inflammatory drug diclofenac and its five related substances. The selected operative mode consisted in microemulsion electrokinetic chromatography with the addition of methyl-β-cyclodextrin. The critical process parameters included both the mixture components (MCs) of the microemulsion and the process variables (PVs). The MPV approach allowed the simultaneous investigation of the effects of MCs and PVs on the critical resolution between diclofenac and its 2-deschloro-2-bromo analogue and on analysis time. MPV experiments were used both in the screening phase and in the Response Surface Methodology, making it possible to draw MCs and PVs contour plots and to find important interactions between MCs and PVs. Robustness testing was carried out by MPV experiments and validation was performed following International Conference on Harmonisation guidelines. The method was applied to a real sample of diclofenac gastro-resistant tablets.
Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: serena.orlandini@unifi.it.
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Orlandini
Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
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Pasquini
Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
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Caprini
Department of Chemistry "U. Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Florence, Italy.
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Del Bubba
Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
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Squarcialupi
Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
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Colotta
Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: sandra.furlanetto@unifi.it.
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Furlanetto
D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D002845:Chromatography; D004008:Diclofenac / Q000031:analogs & derivatives / Q000032:analysis* / Q000302:isolation & purification; D019075:Electrophoresis, Capillary; D015203:Reproducibility of Results; D047392:beta-Cyclodextrins / Q000737:chemistry*
D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D004008:Diclofenac
Capillary electrophoresis; Diclofenac; Experimental design; Impurities; Mixture-process variable approach; Quality by design