Preservative and Antimicrobial Agents

In a microorganism prone environment, it is preferable to protect a dressing with a preservative such as chlorhexidine to prevent the contamination of the dressing. It is necessary to consider the solubility of an agent in the liquid phase of the dressing during the selection of an antimicrobial agent. The formulated polyvinyl acetate and polybutyral materials were dissolved in ethanol that is also a solvent for chlorhexidine diacetate. The information (Block, 2001) in Table 2.12 provides solubilities of chlorhexidine compounds in different solvents. 

From inspection of Table 2.12, it is apparent that only chlorhexidine diacetate is sufficiently soluble in ethanol, so the liquid applied barrier dressing consisting of polymers dissolved in ethanol must be preserved by chlorhexidine diacetate, because water is not an option. The concentration of this agent is another consideration, but the range of options is clear from the above table. 

Chlorhexidine compound Water Ethanol at 2-Propanone (20°C) Dichloromethane 

Sources Principles and Practices of Disinfection, Preservation, and Sterilization, S. S. Block, ed., Blackwell Scientific Publications, St. Louis, 1982 Disinfection, Sterilization, and Preservation, S. S. Block, ed., 5th ed., Lippincott Williams Wilkins, New York, 2001, pp. 321 

Antibacterial agent Bactericidal Sporicidal (%wt/vol) Bacteriostatic Sporostatic 

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Phenoxyethanol is an antimicrobial preservative used in cosmetics and topical pharmaceutical formulations at a concentration of 0.5-1.0% it may also be used as a preservative and antimicrobial agent for vaccines. Therapeutically, a 2.2% solution or 2.0% cream has been used as a disinfectant for superficial wounds, burns, and minor infections of the skin and mucous membranes. 

Products and Uses A component included as a preservative and antimicrobial agent in cheese spreads (pasteurized), canned fruits, and vegetables. 

In a survey of cosmetic allergy Schorr (1971) mentioned other cosmetic preservatives and antimicrobial agents betaines, miranols (amphoteric), dimethoxane (Dioxin), and dehydroacetic acid. How often they produce allergic reactions is unknown only a few have been reported. Dimethoxane (1.25%) sensitized 50 of 205 subjects in a Draize test (Maibach 1971). 

Preservatives or antimicrobial agents play an important role in today s supply of safe and stable foods. Increasing demand for convenience foods and reasonably long shelf life of processed foods make the use of chemical food preservatives imperative. Some of the commonly used preservatives—such as sulfites, nitrate, and salt—have been used for centuries in processed meats and wine. The choice of an antimicrobial agent has to be based on a knowledge of the antimicrobial... 

Potassium metabisulfite is used in applications similar to those of sodium metabisulfite in pharmaceuticals and in the food, brewing, and wine making industries. It is used as an antioxidant, antimicrobial preservative and sterilizing agent. 

In the food industry and in wine production, sodium metabisulfite is similarly used as an antioxidant, antimicrobial preservative, and antibrowning agent. However, at concentrations above about 550 ppm it imparts a noticeable flavor to preparations. 

Antimicrobial agents are known to be protein inhibitors therefore, it is important to titrate the amount of the agent to act as a preservative. This preservative must be able to kill or inhibit microbial agents that could contaminate the product and adulterate it. The other issue is that the concentration of the preservative or antimicrobial agent may inhibit the protein drug. A significant amount of laboratory time must be devoted to this project—much more than a unit dose will require. 

Products and Uses An emulsifier, film former, stabilizer, suspending agent, and thickening agent. Used as a food additive, preservative, and antimicrobial. 

Products and Uses An ingredient used in perfumes, artificial fruit flavors, breads, and grains. Antimicrobial agent, flavoring agent, mold inhibitor in bread, preservative, and emulsifying agent (stabilizes and maintains mixes). 

To highlight the method development plan, we will look at a series of preservatives known as parabens. These preservatives are used in the cosmetic, pharmaceutical, and food industries and are effective antifungal and antimicrobial agents. Antifungal and antimicrobial activity increases with increasing chain length. Methyl and propyl parabens can be added directly to foodstuffs in most countries, and ethyl paraben is permitted in some countries. They can be incorporated into foods at a maximum level of 0.1%. Parabens do occur naturally, but those used in industry are synthetic analytes produced by the esterification of parahydroxbenzoic acid with a suitable alcohol. For example, methanol would be used in the manufacture of methyl parahydroxybenzoate. We have chosen to look at a subsection of the paraben series that includes... 

Microorganisms (MO) are a common source of OF in foods [127]. If the product is not sterile (via heating or irradiation), or preserved via antimicrobial agents (e.g., humectants or chemical preservatives), microorganisms may grow in the product and produce OF. 

Acidulant Organic compound used to acidify or lower pH. They are food additives used to activate chemical leavening agents and act synergistically with preservatives or antimicrobial agents. 

The key markets for quaternaries are as swimming pool algaecides and in cooling water appHcations (see Water, treatment of swimming pools, spas, AND HOTTUBs), which further explains their importance as process biocides rather than preservatives. Some uses in latex films and plastics have been claimed (14,15). Primary quaternary ammonium industrial antimicrobial agents and their producers are presented in Table 4. 

Miscellaneous, New, and Developmental Antimicrobial Agents. Table 11 shows some of the antimicrobials that do not neady fit into the principal families. Acrolein (qv) is a unique chemical used for secondary oil recovery (43). Biobor has become the antimicrobial addition of choice for aviation fuels (44). Cbloropbtbalonil (tetrachloroisophthalnitrile [1897-45-6]) is a significant agricultural fungicide, in addition to being one of the most important latex paint film preservatives (producer, ISK). 

Sulfur dioxide, sulfites, and metabisulfites have had extensive use as antimicrobial preservatives in the food industry. In pharmaceuticals they have had a dual role, acting as preservatives and antioxidants. The sulfa dmgs, or sulfonamides, the first effective chemotherapeutic agents to be employed... 

The intended application of an antimicrobial agent, whether for preservation, antisepsis or disinfection, will influence its selection and also affect its performance. For example, in medicinal preparations the ingredients in the formulation may antagonize preservative activity. The risk to the patient will depend on whether the antimicrobial is in close contact with a break in the skin or mucous membranes or is introduced into a sterile area of the body. 

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

Large-volume parenterals (LVPs) and small-volume parenterals (SVPs) containing no antimicrobial agent should be terminally sterilized. It is common practice to include an antimicrobial agent in SVPs that cannot be terminally sterilized or are intended for multiple-dose use. The general exceptions are products that pass the USP Antimicrobial Preservative Effectiveness Test [1] because of the antimicrobial activity of the active... 

Ayala-Zavala JF, del-Toro-Sanchez L, Alvarez-Parrilla E, Soto-Valdez H, Martin-Belloso O, Ruiz-Cruz S and Gonzalez-Aguilar GA. 2008b. Natural antimicrobial agents incorporated in active packaging to preserve the quality of fresh fruits and vegetables. Stewart Postharvest Rev 4 1—9. 

Tributyltin acetate, (C4H9)3SnOOCCH3, and bis(tributyltin) oxide, (C4H9)3Sn-0-Sn(C4H9>3, have been commercialized as antimicrobial agents in the paper, wood preservation, plastics and textile industries29. 

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