The application of pharmaceutical quality by design concepts to evaluate the antioxidant and antimicrobial properties of a preservative system including desferrioxamine |
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| Authors: | Má rcia Lombardo,Breno Pannia Espó sito,Felipe Rebello Lourenç o,Telma Mary Kaneko |
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| Affiliation: | 1.Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil ;2.Center of Drugs, Cosmetics and Sanitizing Products, Adolfo Lutz Institute, São Paulo, Brazil ;3.Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil |
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| Abstract: | BackgroundThe purpose of the present study was to investigate the antioxidant and antimicrobial activities of a conventional preservative system containing desferrioxamine mesylate (DFO) and optimize the composition of the system through mathematical models.MethodsDifferent combinations of ethylenediaminetetraacetic acid (EDTA), sodium metabisulfite (SM), DFO and methylparaben (MP) were prepared using factorial design of experiments. The systems were added to ascorbic acid (AA) solution and the AA content over time, at room temperature and at 40 °C was determined by volumetric assay. The systems were also evaluated for antioxidant activity by a fluorescence-based assay. Antimicrobial activity was assessed by microdilution technique and photometric detection against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus brasiliensis. A multi-criteria decision approach was adopted to optimize all responses by desirability functions.ResultsDFO did not extend the stability of AA over time, but displayed a better ability than EDTA to block the pro-oxidant activity of iron. DFO had a positive interaction with MP in microbial growth inhibition. The mathematical models showed adequate capacity to predict the responses. Statistical optimization aiming to meet the quality specifications of the ascorbic acid solution indicated that the presence of DFO in the composition allows to decrease the concentrations of EDTA, SM and MP.ConclusionDFO was much more effective than EDTA in preventing iron-catalyzed oxidation. In addition, DFO improved the inhibitory response of most microorganisms tested. The Quality by Design concepts aided in predicting an optimized preservative system with reduced levels of conventional antioxidants and preservatives, suggesting DFO as a candidate for multifunctional excipient.Graphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00370-9) contains supplementary material, which is available to authorized users. |
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| Keywords: | Desferrioxamine Antioxidant Preservative Experimental design Design space |
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