Preservatives quaternary ammonium compounds

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... 

The most widely used preservative remains benzalkonium chloride, which often is supplemented with disodium edetate. The benzalkonium chloride defined in the USP monograph is the quaternary ammonium compound alkylbenzyldimethylammonium chloride, in which the alkyl portion is composed of a mixture of chain lengths ranging from C8 to C16. This compound s popularity is based, despite its compatibility limitations, on its being the most effective and rapid-acting preservative with excellent chemical stability. It is stable over a wide pH range and does not... 

Preservatives such as sodium benzoate, sorbic acid, and methyl and propyl parabens have been used in liquid and semisolid dosage forms. There have been reports that the parabens have been inactivated when used in the presence of various surfactants. This loss of activity was thought to be due to the formation of complexes between the preservative and the surfactant. The interaction between polysorbate (Tween) 80 and the parabens has been demonstrated by a dialysis technique (Ravin and Radebaugh, 1990). It has also been shown that molecular complexes form when the parabens are mixed with polyethylene glycol (PEG) and methylcellulose. The degree of binding was less than that observed with Tween 80. Sorbic acid also interacts with Tweens but does not interact with PEGs. The quaternary ammonium compounds are also bound by Tween 80, which reduces their preservative activity. 

Commonly used preservative agents include organic acids such as benzoic acid and salts, the parabens, (alkyl esters ofp-hydroxybenzoic acid), sorbic acid and salts, phenolic compounds, quaternary ammonium compounds, alcohols, and mercurials such as thimerosal in 0.001-0.004% concentration. 

Studies with preservatives have shown that some combinations are more effective than are the individual constituents alone. Thus, a combination of EDTA and quaternary ammonium compounds is effective [60,63,124]. Also, phenyl mercuric nitrate and phenylethanol, chlorocresol and phenylethanol and EDTA and chlorocresol [124] all show enhanced activity. Polysorbate 80 enhances the activity of polymyxin against Ps. aeruginosa [97] but, unlike EDTA, is unable to enhance the activity of most other agents. 

An ideal preservative that meets all the requirements does not exist. The choice must be made on an individual basis, balancing antimicrobial efficacy against safety. The antimicrobial preservatives are classified into four major types acidic, neutral, mercurial, and quaternary ammonium compounds (Table 6). Frequently, a combination of two or more of these preservatives is needed to achieve the desired efficacy. 

The other three classes of preservatives have been widely used in ophthalmic, nasal, and parenteral products, but not frequently in oral liquid preparations. The neutral preservatives are volatile alcohols their volatility introduces problems of odor and loss of preservative on aging in multidose preparations. The mercurials and quaternary ammonium compounds are excellent preservatives but are subject to incompatibilities.Mercurials are readily reduced to free mercury, and the quaternary compounds are inactivated by anionic substances. 

Definable in chemical terms Many of the existing preservatives, such as the quaternary ammonium compounds, are mixtures of various homologues. Often the activity obtained is a function of the mixture composition. Unless it is possible to define and control mixture composition, the performance of the agents will be variable, even if they conform to a pharmacopoeia specification. 

Benzalkonium chloride is a quaternary ammonium compound used in pharmaceutical formulations as an antimicrobial preservative in applications similar to other cationic surfactants, such as cetrimide. 

Benzethonium chloride is a quaternary ammonium compound used in pharmaceutical formulations as an antimicrobial preservative. Typically, it is used for this purpose in injections, ophthalmic and otic preparations at concentrations 0.01-0.02% w/v. Benzethonium chloride may also be used as a wetting and solubilizing agent, and as a topical disinfectant. 

Antimicrobial activity benzyl alcohol is bacteriostatic and is used as an antimicrobial preservative against Gram-positive bacteria, molds, fungi, and yeasts, although it possesses only modest bactericidal properties. Optimum activity occurs at pH below 5 little activity is shown above pH 8. Antimicrobial activity is reduced in the presence of nonionic surfactants, such as polysorbate 80. However, the reduction in activity is less than is the case with either hydroxybenzo-ate esters or quaternary ammonium compounds. The activity of benzyl alcohol may also be reduced by incompatibilities with some packaging materials, particularly polyethylene see Section 12. 

Cetrimide is a quaternary ammonium compound that is used in cosmetics and pharmaceutical formulations as an antimicrobial preservative see Section 10. It may also be used as a cationic surfactant. In eye-drops, it is used as a preservative at a concentration of 0.005 % w/v. 

Imidurea is compatible with other preservatives including sorbic acid and quaternary ammonium compounds. It is also compatible with other pharmaceutical and cosmetic excipients including proteins, nonionic surfactants, and lecithin. ... 

Incompatible with aluminum and other metals, strong oxidizing agents, strong acids and bases, sodium chloride solutions, lecithin, phenylmercuric compounds, quaternary ammonium compounds, thioglycolate, and proteins. The presence of sodium metabisulfite, edetic acid, and edetates in solutions can reduce the preservative efficacy of thimerosal. ... 

Many cosmetics, paints, ointments, foods, shampoos, and medicines contain preservatives to combat biological degradation. Toxic chemicals used as preservatives include mercury compounds, formaldehyde, methyl and propyl p-aminobenzoic acids, butylated hydroxyanisol, butylated hydroxytoluene, benzoic acid, and quaternary ammonium compounds. 32 ... 

The shift to preservatives based on copper, azoles, and quaternary ammonium compounds has lessened the risk associated with wood preservatives. However, all wood preservatives contain ingredients that pose some degree of risk to non-target organisms, and the public and regulatory perception of a proper balance between risk and benefit is steadily changing (Brooks, 2002 Lebow et al., 2002). Preservative ingredients that are considered acceptable today may be considered as less desirable in the future. 

One problem that may arise is when an antibiotic or preservative is the product, or part of the product under test. When this happens, the material must be inactivated or removed before sterility testing can take place. There are several methods of achieving this. Antibiotics, such as the penicillins, may be inactivated by the addition of the enzyme P-lactamase, whilst the action of sulphonamides can be blocked by the addition of />-aminobenzoic acid. Products containing preservatives or antimicrobial agents, such as benzoic acid, alcohols, or phenols, are diluted to the level at which the compound becomes ineffective. Products containing quaternary ammonium compounds can be inactivated by the addition of Tween, whilst many compounds containing heavy metals can be... 

A number of fatty amines and their derivatives, especially quaternary ammonium compounds, are widely used in formulations for the control of bacteria, fungi, viruses and algae, in disinfectant/sanitizers and wood-preservation applications. Table 14.3 presents the fatty amines and derivatives which are frequently used in biocidal formulations. 

The use of quaternary ammonium compounds as biocides in wood preservation formulations is increasing rapidly. Their low toxicity and biodegradable properties, combined with their favourable adsorption characteristics, have led to an increase in the popularity of these products as an alternative to other wood preservative formulations such as pentachloraphenate (PCP) and chromated copper arsenate (CCA). Due to growing environmental pressure, the use of these latter products is declining and the development of alternative wood preservatives is gaining momentum. 

Used by themselves, or in combination with other modem biocides - such as systematic fungicides, bactericides or insecticides - the long-alkyl-chain quaternary ammonium compounds offer a useful tool in the development of new environmentally acceptable wood preservative formulations. The most commonly used quaternary ammonium compounds are coco(fractionated) benzyldimethylammonium chloride and didecyldimethylammonium chloride. 

Benzalkonium chloride is the most widely used preservative in ophthalmology. It is a quaternary ammonium compound that acts as an antimicrobial agent by denaturing proteins and disrupting cytoplasmic membranes. 

Quaternary ammonium compounds are cationic detergents. They are used as preservatives in cosmetic and medical topical products and also as a disinfectant for the skin (for instance, preoperative skin cleaning). It is also known as an algaecide (wood preservative, some marine paints). Patch-test concentrations range from 0.01% to 0.1% aqua. Patch testing with 0.1% aqua easily provokes irritant reactions true allergic responses are also obtained with 0.01% aqua. Crossreactions between the quaternary ammonium compounds are frequently seen. 

Dowicil 100, Dowicil 75, Dowicide Q, CAS no. 4080-31-3). This is a quaternary ammonium compound and a formaldehyde releaser. It is used mainly in water-based cosmetics, as a preservative (Jacobs et al. 1995 Boffa and Beck 1996 Prue et al. 1998). The patch-test concentration is 2% pet. 

Quaternium 15 is a quaternary ammonium compound, used as a broad-spectrum formaldehyde-releasing bactericide agent. It is contained as a preservative in cosmetics and toiletries. Case reports included hairdressers, a beautician and an engineer working on the maintenance of machinery in a chicken processing plant. 

Ci6-alkylpyridinium chloride Pyrisept Uses quaternary ammonium compound used as a preservative in cosmetics and pharmaceuticals topical anti-infective and disinfectant used on the surface of latex gloves A... 

Uses fixative for perfumes, a bactericide [in conjunction with i,2-dibromo-2,4-dicyanobutane (Euxyl K 400) and quaternary ammonium compounds], an insect repellent, a topical antiseptic, a solvent for cellulose acetate, dyes, inks, and resins in organic synthesis of plasticizers in germicides in pharmaceuticals in cosmetics in preservatives. PHENOXYETHANOL... 

As the effectiveness against bacteria is weak, weaker than the activity against moulds, 2-phenyl ethanol is in general applied in combination with other microbicides, e.g. with p-hydroxy-benzoic acid esters (Section 6.1.10), quaternary ammonium compounds (Section 16-1), p-chloro-m-cresol (Section 5.3.1) for the preservation of cosmetic and pharmaceutical products. It is especially effective in acidic media. 

Neither anionic nor non-ionic surfactants impair Bronopol s antimicrobial efficacy. For that reason the product is a most suitable preservative for detergent solutions, bath foams, shampoos and hair rinses. Bronopol is also compatible with quaternary ammonium compounds (Section 16.1) and cationic active ingredients such as benzalkonium chloride. 

The antimicrobial efficacy of the amine-formaldehyde reaction products essentially corresponds to the formaldehyde content of these compounds. Known exceptions are HTA, hexahydro-oxadiazines and octahydro-s-tetrazines, which derive from ammonia respectively certain alkylolhydrazines (Paulus, 1980) here the detection of formaldehyde by the Taimenbaum methods gives a negative result, which means that these substances have no significant antimicrobial effect at neutral to alkaline pH they release formaldehyde in acidic media only. This pH dependency is broken off, if, for example, HTA is quatemized (Jacobs et al., 1916). In contrast to HTA the quaternary hexaminium salts release formaldehyde widely independent of pH and therefore may be used as preservatives also for media of neutral to alkaline pH. They are not comparable with the surface active conventional quaternary ammonium compounds (QACs see Section 16.1)... 

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