Lourenço Felipe Rebello, Francisco Fabiane Lacerda, Ferreira Márcia Regina Spuri, Andreoli Terezinha De Jesus, Löbenberg Raimar, Bou-Chacra Nádia
Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
J Pharm Pharm Sci. 2015;18(3):551-61. doi: 10.18433/j3j600.
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.
必须优化防腐剂的使用，以确保抗菌系统的有效性以及产品安全性。尽管防腐剂种类繁多，但其组合的协同或拮抗作用尚未得到充分证实，这仍然是制药和化妆品开发中的一个问题。本文的目的是采用单纯形重心法建立一种空间设计，以实现乳液化妆品中三种防腐剂（对羟基苯甲酸甲酯、对羟基苯甲酸丙酯和咪唑烷基脲）和乙二胺四乙酸（EDTA）的最低有效浓度。制备了22种仅在咪唑烷基脲（A：0.00至0.30%w/w）、对羟基苯甲酸甲酯（B：0.00至0.20%w/w）、对羟基苯甲酸丙酯（C：0.00至0.10%w/w）和EDTA（D：0.00至0.10%w/w）浓度上有所不同的乳液配方。它们分别进行测试，并进行二元、三元和四元组合测试。将这些配方的等分试样接种几种微生物。采用电化学方法在接种后以及接种后2、4、8、12、24、48和168小时测定微生物负荷。采用优化策略来获得防腐剂和EDTA的浓度，从而同时形成对所有微生物最有效的防腐体系。组合使用防腐剂和EDTA具有对更广泛的微生物谱表现出潜在协同作用的优势。基于图形和优化策略，我们提出了一种含有四元组合（A：55%；B：30%；C：5%和D：10%w/w）的新配方，该配方符合常规挑战试验的规范。一种设计空间方法成功地用于优化乳液化妆品中防腐剂和EDTA的浓度。
