2005 ANNUAL SCIENTIFIC SEMINAR 359 STRATEGIES OF PRESERVATION Donald J. English Avon Products, Inc., Suffern, NY 10901 Introduction A preservative is a chemical agent that will either kill or prevents the growth of microorganisms that are introduced during consumer usage in those product formulations that are susceptible to microbiological contamination in order to prevent adverse risks for both the user and the formulation itself To prevent microbial contamination of product formulations during consumer usage, there are certain strategies of preservation that need to be evaluated before a preservative system is incorporated into a product formulation. Regulatory Status of Preservatives Before selecting a preservative, it is important to determine whether a preservative can be used ill a formulation that could be sold in a particular country or geographic region. The problem is that not all preservatives can be used in all countries. For example, the European Comrnwtities Cosmetic Directive and the Japanese Ministry of Health and Welfare have always regulated the use of preservatives in cosmetic products by having positive lists. However, preservatives are not regulated in the United States other than that the Food and Drug Administration (FDA) requires that manufacturers have substantiated their safe use in cosmetic products. However, the FDA does have the ability to restrict or prohibit the use of a preservative due to safety reasons. In the absence of an official United States preservative list, the Cosmetic Ingredient Review (CIR) reviews and assesses the safety of cosmetic ingredients such as preservatives. Due to the discrepancies in whether a preservative can or cannot be used in a particular geographic region or country, a cosmetic company has to be diligent when formulating products with preservatives. Formulation Factors The following formulation factors can have an affect on preservative activity: water activity of a product formulation, pH of a product formulation and solubility of preservatives. Microorganisms need a source of water for cellular metabolism and growth. By reducing the amount of water in a formulation, microorganisms will be affected by having a longer generation time or reduce metabolic activity. Water activity is different from water content of a formulation. Water activity is a measurement that is used to determine the amount of wtbounded water in a system that is necessary to sustain the metabolism and growth of microorganisms. Water activity can be used as a risk assessment tool to identify those product formulations that are susceptible to microbial contamination during consumer usage. For example, nail enamels, lipsticks and powders are examples of product formulations that have low water activity readings and are less susceptible to microbial contamination because they are anhydrous. Creams and lotions are examples of product formulations that have high water activity readings and are susceptible to microbial contamination because they usually contain high concentrations of water. Besides using preservatives, a slight reduction in the water activity of a formulation can be helpful in preventing the growth of microorganisms by increasing the lag phase of the microbial growth cycle. Examples of ingredients that can be used to lower the water activity level of a product formulation by absorbing water are as follows: glycerol, butylene glycol, propylene glycol, dextrin, xanthan gum, sodium chloride, and ethanol. By using a high sugar concentration (e.g. glucose, sucrose, sorbitol), it can also decrease the water activity of a formulation, but also cause an increase in the osmotic pressure. Most microorganisms are able to proliferate at a pH between 4.0 and 10.0. However, there are some microbial species that can grow below and above this pH range. For bacteria, the optimum pH for growth is between 5.5 and 8.5. For yeast and mold, the optimum pH for growth is between 4.0 and 6.0. If a product formulation has a pH below 4.0 or greater than 10.0, there may be no need to include a preservative because the function of many microbial enzymes is pH dependent. In addition, the pH of a formulation may contribute in making injured cells more susceptible to the antimicrobial activity of preservatives. Besides affecting the growth of microorganisms, the pH of a formuJation can affect the antimicrobial activity or the chemical stability of many preservatives.

360 JOURNAL OF COSMETIC SCIENCE The solubility of preservatives is an important factor to consider in preserving product formulations because microorganisms will proliferate only in the aqueous phase of a formulation. Some preservatives are water-soluble and can be added directly to the aqueous phase of a formulation. While there are other preservatives that have limited water solubility, a water miscible solvent has to be used to dissolve them or use heat in order to incorporate them into the aqueous phase. In addition, there are preservatives that are more soluble in oil than in water and will partition themselves between the aqueous and oil phases of an emulsion. It is important to control the partition coefficient of these preservatives that exhibit both oil and water solubility to have an adequately preserved product formulation. Microbiological Activity of Preservatives When using preservatives, it is important to known the antimicrobial spectrum and recommended use concentration of a preservative or preservative system. There are very few preservatives that have a very broad spectrum of antimicrobial activity against both bacteria and fungi. Most preservatives have either good antimicrobial activity against bacteria or fungi. It is important to incorporate a combination of preservatives by using 2 or more types of preservatives or a preservative blend into a product formulation that will provide antimicrobial activity against both bacteria and fungi contamination. Furthermore, the concentration of a preservative in a formulation may determine if the antimicrobial activity is either cidal or inhibitory towards microorganisms. The minimum concentration for a preservative to prevent or inhibit the growth of a microorganism is known as the Minimum Inhibitory Concentration (MIC). The minimum preservative concentration for cidal activity against a microorganism is known as the Minimum Lethal Concentration (MLC). The MIC and MLC test data for a preservative is used to determine the spectrum of antimicrobial activity and use concentration in a product formulation. From this test data, it is important that the preservative in a formulation is at a sufficient concentration to have either cidal or inhibitory antimicrobial activity to prevent the growth or survivability of microorganisms in a product formulation. Ingredients Affecting Preservatives There are many raw ingredients that can affect the antimicrobial activity of preservatives. Besides a source of water, microorganisms need a source of microbial nutrients to proliferate in a formulation. With the presence of microbial nutrients, it could make a formulation more difficult to preserve because there is now an available source of nutrients for microbial proliferation and/or inactivate preservatives. There are also many raw ingredients that can give physical protection to microorganisms, chemically react, absorb or bind with a preservative to cause inactivation of the antimicrobial activity. Besides using preservatives to protect a formulation against microbial contamination, there are also raw ingredients that are able to enhance or increase the antimicrobial activity of a preservative system in a product formulation such as chelating agents, antioxidants, humectants, emollients, essential oils and fragrances. Processing Conditions The actual manufacturing conditions for a formulation need to be considered to have an adequately preserved product formulation. If the incorrect order of addition for a preservative is done during manufacturing, it may effect the partitioning of a preservative between the water and oil phases of an emulsion. The addition of emulsifying agents to a product suspension should always be performed first in order to coat the solid particles that would be able to absorb preservatives. Preservatives should always be added to a formulation at the appropriate pH to prevent decomposition or to have antimicrobial activity. The addition of a preservative to a batch at the incorrect temperature during processing may have an affect on the actual physical stability of a preservative in a formulation. Packaging The packaging in which a product formulation is going to be filled into is an important consideration when selecting a preservative system. There are many known examples in how the chemical composition of a product package will have an effect on the stability of the preservative system in a product formulation. The type of product package (e.g. tube, pump, aerosol can,jar) may pose an increase in the risk for the occurrence of microbial contamination to the product during consumer use by overwhelming the preservative system. A risk assessment needs to be performed to determine whether the configuration of the packaging can make an adequately preserved product formulation susceptible to microbial contamination during use by the consumer.