Preservatives chlorhexidine

Ethanol and 2-propanol have also found use ia disinfecting clinical thermometers, and as preservatives to prevent microbial deterioration of cosmetics and mediciaals. They are sometimes combiaed with other disiafectants, namely formaldehyde (69), phenoHcs (70), chlorhexidine (71), hypochlorite (72), and phenols (70). 

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... 

In the weakly acidic preservatives, activity resides primarily in the unionized molecules and they only have significant efficacy at pHs where ionization is low. Thus, benzoic and sorbic acids (pKa = 4.2 and 4.75, respectively) have limited preservative usefulness above pH 5, while the 4(p)-hydroxybenzoate esters with their non-ionizable ester group and poorly ionizable hydroxyl substituent (pKa ca. 8.5) have moderate protective effect even at neutral pH levels. The activity of quaternary ammonium preservatives and chlorhexidine probably resides with their cations and are effective in products of neutral pH. Formulation pH can also directly influence the sensitivity of microorganisms to preservatives (see Chapter 11). 

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

Although this chapter is directed toward ophthalmic products, it is largely applicable to parenteral and even nonsterile products (solutions, emulsions, and suspensions). The choice of preservative is limited to only a few chemicals that have been found, over the years, to be safe and effective for this purpose. These are benzalkonium chloride, thimerosal, methyl- and propylparaben, phenylethanol, chlorhexidine,... 

Polyvinyl acetate-vinyl alcohol copolymer dressing with 1.2 chlorhexidine preservative... 

Polyvinyl butyral terpolymer dressing with 1.2% chlorhexidine. Preservative (based on polymer weight)... 

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. 

Microbial degradation of biocides has been described by Hugo [72] who points out that soil organisms are able to break down substances such as phenols added as fumigants. He also reviewed the utilization by bacteria of aromatic compounds (including the preservatives cresol, phenol, benzoic acid and esters of 4-hydroxybenzoic acid). Several types of preservatives and disinfectants, such as the QACs (e.g. cetrimide, cetylpyridinium chloride, benzalkonium chloride), chlorhexidine and phenylethanol can also be inactivated. Significantly, this only occurs at concentrations well below inhibitory or in-use concentrations [33] and thus cannot be responsible for insusceptibility. A further comment about chlorhexidine is given below. 

Bmstein NL. Preservative cytotoxic threshold for benzalkonium chloride and chlorhexidine digluconate in cat and rabbit corneas. Invest Ophthalmol Vis Sci 1980 19 308-313. 

Use of preserved tear substitutes with contact lenses is a concern because the preservatives may bind to the lens polymer, prolonging ocular retention and exposure, which may result in toxic or hypersensitivity reactions. BAK is more readily absorbed than are thimerosal and chlorhexidine in most hydrogel lenses. 

Chlorhexidine salts are widely used in pharmaceutical formulations in Europe and Japan for their antimicrobial properties. Although mainly used as disinfectants, chlorhexidine salts are also used as antimicrobial preservatives. 

As excipients, chlorhexidine salts are mainly used for the preservation of eye-drops at a concentration of 0.01% w/v generally the acetate or gluconate salt is used for this purpose. Solutions containing 0.002-0.006% w/v chlorhexidine gluconate have also been used for the disinfection of hydrophilic contact lenses. 

Chlorhexidine and its salts are widely used, primarily as topical disinfectants. As excipients, chlorhexidine salts are mainly used as antimicrobial preservatives in ophthalmic formulations. 

Oelschlager H, Canenbley R. Clear indication of chlorhexidine dihydrochloride precipitate in isotonic eye-drops report based on experience on the use of chlorhexidine as a preservative. Pharm Ztg 1983 128 1166-1168. 

Concentrations of about 15% of nonionic emulsifying wax are commonly used in creams, but concentrations as high as 25% may be employed, e.g., in chlorhexidine cream BP. Nonionic emulsifying wax is particularly recommended for use with salts of polyvalent metals and medicaments based on nitrogenous compounds. Creams are susceptible to microbial spoilage and should be adequately preserved. 

Preservatives and disinfectants. Many preservatives and disinfectants can be metabolized by a wide variety of Gram-negative bacteria, although most commonly at concentrations below their effective use levels. Growth of pseudomonads in stock solutions of quaternary ammonium antiseptics and chlorhexidine has resulted in infection of patients. Pseudomonas spp. have metabolized 4-hydroxy-benzoate ester preservatives contained in eye-drops and caused serious eye infections, and have also metabolized the preservatives in oral suspensions and solutions. In selecting suitable preservatives for formulation, a detailed knowledge of the properties of such agents, their susceptibility to contamination and limitations clearly provides invaluable information. 

Changes in the efficacy of preservatives vary exponentially with changes in concentration. The effect of changes in concentration (concentration exponent, t, Chapter 11) varies with the type of agent. For example, halving the concentration of phenol (r) = 6) gives a 64-fold (26) reduction in killing activity, while a similar dilution for chlorhexidine (r = 2)... 

Staph, aureus, whereas a 1 50000 dilution prevents growth of Vs. aeruginosa. Reports of pseudomonad contamination of aqueous chlorhex-idine solutions have prompted the inclusion of small amounts of ethanol or isopropanol. Chlorhexidine is ineffective at ambient temperatures against bacterial spores and M. tuberculosis. Limited antifungal activity has been demonstrated which unfortunately restricts its use as a general preservative. Skin sensitivity has occasionally been reported although, in general, chlorhexidine is well tolerated and nontoxic when applied to skin or mucous membranes and is an important preoperative antiseptic. 

In 24-hour collections of urine, glucose maybe preserved by adding 5 mL of glacial acetic acid to the container before starting the collection. The final pH of the urine is usually between 4 and 5, which inhibits bacterial activity. Other preservatives that have been proposed include 5 g of sodium benzoate per 24-hour specimen or chlorhexidine and 0.1% sodium nitrate (NaNs) with 0.01% benzethonium chloride. These may be inadequate, and urine should be stored at 4 °C during collection. Urine samples may lose as much as 40% of their glucose after 24 hours at room temperature. ... 

Solutions formulated to clean hard gas-permeable contact lenses are sterile and pH buffered. They are soaking solutions and include lens-hydrating (wetting) agents (e.g., cationic cellulose derivatives) and preservatives (e.g., edetate disodium, chlorhexidine gluconate). 

Chlorhexidine is also cationic like BKC and exhibits similar incompatibilities. It is not as stable as BKC to autoclaving and may irritate the eyes. It tends to be more favoured in Europe than in the United States, and is particularly used in contact lens products. Chlorobutanol and phenylethyl aclohol are also widely used in ophthalmic products. However, chlorobutanol will hydrolyse in solution, and autoclaving is not usually possible without loss of preservative activity. It is also volatile and may be lost through the walls of plastic containers. 

Preservatives Antimicrobial Benzalkonium chloride Benzyl alcohol Chlorhexidine Imidazolidinyl urea Phenol Potassium sorbate 1 Benzoic acid Bronopol Chlorocresol Paraben esters Phenoxyethanol Sorbic acid Antioxidants a-Tocopherol Ascorbic acid Ascorbyl palmitate Butylated hydroxyanisole Butylated hydroxytoluene Sodium ascorbate Sodium metabisulphite Chelating agents Citric acid Edetic acid... 

Adsorption, where the preservative attaches itself to the surface of a plastic, tends to vary according to the type of plastic, constituents in the plastic, surface treatment, surface area of the plastic. Adsorption has been found with most mercurials, including Thiomersal, benzalkonium chloride and bromide, etc. Small amounts of chlorhexidine, benzoic acid and hydroxybenzoates have also had losses reported for certain plastics. 

Arbcide. [ICI Spec. Chent IQ Surf. Belgium] Chlorhexidine salts preservative, bactericide. 

D. H. Pashley, L. Tjaderhane, Chlorhexidine preserves dentin bond in vitro, J. Dent. Res. 

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