The application of pharmaceutical quality by design concepts to evaluate the antioxidant and antimicrobial properties of
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RESEARCH ARTICLE
The application of pharmaceutical quality by design concepts to evaluate the antioxidant and antimicrobial properties of a preservative system including desferrioxamine Márcia Lombardo 1,2 & Breno Pannia Espósito 3 & Felipe Rebello Lourenço 1 & Telma Mary Kaneko 1 Received: 7 March 2020 / Accepted: 21 August 2020 # Springer Nature Switzerland AG 2020
Abstract Background The 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. Methods Different 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. Results DFO 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. Conclusion DFO 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.
Keywords Desferrioxamine . Antioxidant . Preservative . Experimental design . Design space
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40199-020-00370-9) contains supplementary material, which is available to authorized users. * Márcia Lombardo [email protected] 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
The development of stable compositions is crucial for meeting the quality standards for medicines and cosmetics. Problems affecting the formulation integrity represen
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