74 PRESERVATIVES
Table 1: % Undissociated acid as a function of pH for common organic acids pH
3
Dehydroacetic Acid Benzoic Acid Sorbic Acid Salicylic Acid Levulinic Acid Anisic Acid
Caprylhydroxamic Acid
99.5 94.1 98.3 48.3 97.5 96.9 100
groups attract water. Medium Chain Terminal Diols alone are very effective against bacteria but have difficulty when used alone against yeast and mold. A second hurdle is needed to provide broad spectrum coverage.
Organic acids and chelating agents Organic acids are a component of the Hurdle Technology approach which have been studied since the 1900s. They are often employed in combination with MCTDs to provide increased efficacy against yeast and mould. Benzoic acid is the organic acid that has seen the greatest increase in usage in response to the changing preservation landscape. Other common organic acids that can contribute to antimicrobial efficacy are shown in Table 1. Organic acids can function as
preservatives or preservation boosters in two ways. Organic acids with hydrophobic character can disrupt cell membranes in a similar way to the MCTDs. Organic acids can also be transported across cell membranes or cell walls to affect cell biochemistry and homeostasis. In order to perform the latter function, the organic acid must be present in the undissociated form in the formulation. Essentially all organic acids that are
effective against microbes are weak acids. This means that when dissolved in aqueous solution, they dissociate. As the pH is increased the molecules transition from the dissociated form to the undissociated form. To be effective for preservation, organic acids must be in the undissociated form because only the undissociated form can transport across cell membranes or cell walls and affect cell biochemistry and homeostasis. The amount of undissociated acid may
be determined at any pH from the pKa. The percent of the undissociated acid, which is essentially the ‘active’ form, decreases as a log function of the pH. This is important for determining the appropriate formulation pH for activity. For instance, an organic acid with a pKa of 6 in a formulation with pH of 6 is 50% in its undissociated form, meaning it is 50%
PERSONAL CARE NORTH AMERICA 4
94.9 61.3 84.9 8.5
5
65.1 13.7 36.0 0.9
100
28.5 24.0 100
active. The % undissociated acid as a function of pH is shown in Table 1 for common organic acids used for preservation or as hurdles. Most of these ingredients have a low amount of undissociated acid above pH 5. This can pose a particular challenge for formulation with organic acids as most legacy formulations developed with parabens, isothiazolinones, or phenoxyethanol have a pH near 6.0 – 7.0.
Metal binding and sequestering is another hurdle mechanism for efficacy against microorganisms that can be found in some organic acids. The mode of action of this hurdle is disruption of cell walls by binding metals and sequestering metals, particularly iron, which are required for cell growth.1
Caprylhydroxamic acid is an
organic acid which is a particularly efficient chelating agent. Caprylhydroxamic acid (CHA) has a C8 chain and a hydroxamic acid moiety, which is also a polar group. The structure has many similarities to the Medium Chain Terminal Diols, with a similar degree of hydrophobicity. Based on the chemical structure, it is expected that CHA would have similar behavior in terms of membrane disruption. Caprylhydroxamic acid has also been shown to be a strong chelating agent for Iron III. Being a hydroxamic acid as opposed to a carboxylic acid, CHA has a unique benefit in formulation because it has a much higher pKa. At pH 7, CHA is approximately 99% undissociated which means the amount of the ‘active’ form is significantly higher than other common organic acids, such as benzoic acid. Combining CHA with MCTDs creates a highly effective Hurdle Technology ingredient combination that can provide broad spectrum protection at neutral pH.
Caprylhydroxamic acid and MCTD combinations Combination products of CHA and an MCTD allow formulators to easily add just one material to a formulation and have broad spectrum preservation efficacy using the Hurdle Technology approach. The preservation efficacy of four CHA –
6
15.7 1.6 5.3 0.1 3.8 3.1
99.9 7
1.8 0.2 0.6 0.0 0.4 0.3
99.0
MCTD combinations was evaluated in an SPF 28 water-resistant sunscreen formulation (pH 6.8) using a standard Preservative Efficacy Test method: The material is inoculated with about 105
or 107
colony forming units (CFU) per milliliter. A standard set of 4 test organisms is evaluated; 1 Gram-positive, 1 Gram- negative, 1 yeast, and 1 mold. The materials are incubated and the number of CFU/mL are measured at 2, 7, 14, and 28 day intervals. There are various test criteria against which the preservation efficacy of a system can be measured. The four most popular today are the EP-A criteria, the EP-B criteria, the CTFA (PCPC) criteria, and the ISO11930 criteria. The CHA-MCTD combinations evaluated and the lowest % (w/w) usage level of each combination to pass all four test criteria are presented in Table 2.
Combination of CHA with MCTDs has
proven successful in many formulation types including a range of leave-on and rinse-off formats. Recent innovation with CHA has focused on unique combinations with MCTDs and solvents to develop new Hurdle Technology ingredient blends with additional benefits for formulators.
Cold process alternative preservation Cold process formulation can be desirable for many formulators for a variety of reasons. Processing a formulation without heat has a simplistic benefit of limiting the complexity of a production process. Cold process manufacturing can also provide an energy benefit in both cost savings and contribution to a company’s sustainability footprint. The location of manufacturing sites in cold regions can also require that all ingredients are easily incorporated at low temperatures. This can be particularly true when manufacturing substrate-based products such as wet wipes or facial sheet masks. In many wet substrate manufacturing sites liquid, low viscosity ingredients are required for production. This need drove innovation in CHA-MCTD combinations that required additional solvents and optimisation of CHA and MCTD concentrations. Evaluation of
May 2019
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