title: Design Space Approach for Preservative System Optimization of an Anti-Aging Eye Fluid Emulsion.
abstract: The use of preservatives must be optimized in order to ensure the efficacy of an antimicrobial system as well as the product safety. Despite the wide variety of preservatives, the synergistic or antagonistic effects of their combinations are not well established and it is still an issue in the development of pharmaceutical and cosmetic products. The purpose of this paper was to establish a space design using a simplex-centroid approach to achieve the lowest effective concentration of 3 preservatives (methylparaben, propylparaben, and imidazolidinyl urea) and EDTA for an emulsion cosmetic product. Twenty-two formulae of emulsion differing only by imidazolidinyl urea (A: 0.00 to 0.30% w/w), methylparaben (B: 0.00 to 0.20% w/w), propylparaben (C: 0.00 to 0.10% w/w) and EDTA (D: 0.00 to 0.10% w/w) concentrations were prepared. They were tested alone and in binary, ternary and quaternary combinations. Aliquots of these formulae were inoculated with several microorganisms. An electrochemical method was used to determine microbial burden immediately after inoculation and after 2, 4, 8, 12, 24, 48, and 168 h. An optimization strategy was used to obtain the concentrations of preservatives and EDTA resulting in a most effective preservative system of all microorganisms simultaneously. The use of preservatives and EDTA in combination has the advantage of exhibiting a potential synergistic effect against a wider spectrum of microorganisms. Based on graphic and optimization strategies, we proposed a new formula containing a quaternary combination (A: 55%; B: 30%; C: 5% and D: 10% w/w), which complies with the specification of a conventional challenge test. A design space approach was successfully employed in the optimization of concentrations of preservatives and EDTA in an emulsion cosmetic product.
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Felipe Rebello
authors.initials: FR
authors.lastname: Lourenço
authors.forename: Fabiane Lacerda
authors.initials: FL
authors.lastname: Francisco
authors.forename: Márcia Regina Spuri
authors.initials: MR
authors.lastname: Ferreira
authors.forename: Terezinha De Jesus
authors.initials: Tde J
authors.lastname: Andreoli
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
authors.forename: Nádia
authors.initials: N
authors.lastname: Bou-Chacra
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D002626:Chemistry, Pharmaceutical; D015169:Colony Count, Microbial / Q000379:methods; D003358:Cosmetics / Q000008:administration & dosage / Q000138:chemical synthesis*; D015195:Drug Design; D004655:Emulsions / Q000008:administration & dosage / Q000138:chemical synthesis*; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000138:chemical synthesis*; D015595:Skin Aging / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D003358:Cosmetics; D004655:Emulsions; D011310:Preservatives, Pharmaceutical