Preservatives availability

Preservative availability may be appreciably reduced by interaction with packaging materials. Examples include the permeation of phenolic preservatives into the rubber wads and teats of multi-dose injection or eye-drop containers and by their interaction with flexible nylon tubes for creams. Quaternary ammonium preservative levels in formulations have been significantly reduced by adsorption onto the surfaces of plastic and glass containers. Volatile preservatives such as chloroform are so readily lost by the routine opening and closing of containers that their usefulness is somewhat restricted to preservation of medicines in sealed, impervious containers during storage, with quite short use lives once opened. 

The formulation scientist must be aware of interactions between preservatives and other components of a formulation that could compromise the efficacy of the preservative. For example, proteins can bind thi-merosal, reducing preservative efficacy. Partitioning of preservative into a micellar phase or an oil phase (in an emulsion) can also reduce the effective concentration of preservative available for bactericidal or bacteriostatic action. Preservative efficacy testing should be done on the proposed formulation to assure an effective preservative concentration. 

National Center for Home Food Preservation. Available from . 

For this reason, a drug product that is to be used multiple times (multidose) must contain a preservative to prevent bacterial growth. A list of preservatives that have been used in pharmaceutical formulations is shown in Table 2. However, most of these are not usually compatible with protein formulations. Some, such as the parabens, are not active in the presence of nonionic surfactants—excipients that are typically required in protein formulations.Others may not be acceptable for a particular route of administration. Benzalkonium chloride, a commonly used preservative in topical formulations, causes ototoxicity when applied to the ear. As with buffering species, the list of preservatives available to the formulation scientist quickly narrows to just a few compounds including benzyl alcohol, phenol, w-cresol, and benzethonium chloride. A benzyl alcohol-containing formulation of epoetin alfa has been shown to be stable, even when dispensed in plastic syringes. ... 

Kazmi SJA, Mitchell AG. Preservation of solubilized and emulsified systems I correlation of mathematically predicted preservative availability with antimicrobial activity. J Pharm Sci 1978 67 1260-1266. 

Chapman DG. Preservatives available for use. In Board RG, Allwood MC, Banks JG, eds. Preservatives in the Food, Pharmaceutical and Environmental Industries. Oxford Blackwell Scientific, 1987. 

Phenylmercuric acetate is no longer permitted to be used as a pesticide in the USA. It is, however, included in the FDA Inactive Ingredients Guide (ophthalmic preparations), and is also included in nonparenteral medicines licensed in the UK. In France, a maximum concentration of 0.01% is permitted for use in pharmaceuticals. The use of phenylmercuric acetate in cosmetics is restricted in the UK see Phenylmercuric Nitrate. Included in the Canadian List of Acceptable Non-medicinal Ingredients (however, there must be no other suitable preservatives available). 

Tip Look for rice vinegar without preservatives, available at most health food stores. 

The law governing the sale of milk in this country enacts that the content of fat (cream) shall be not less than 3 per cent. The various preservatives available for use are either prohibited, or are restricted as to the quantity that... 

Preservative Available with or without 0.1% para-methoxyohenol Watar Less than 0.05% by Karl Fischer titration Ultraviolet absorbance ... 

Because it provides highly effective antimicrobial activity at low concentrations, DOWICIL 75 is one of the most cost-effective aqueous- system preservatives available. 

Several international organizations have been estabUshed that can offer conservation advice or even practical help in areas of the world where such is not readily available. The International Centre for the Study of the Preservation and the Conservation of Cultural Properties (ICCROM), based in Rome, is an intergovernmental organization that serves over 80 member states, among which is the United States. In the United States, the National Institute for Conservation of Cultural Property (NIC) serves as a fomm to faciUtate information distribution and exchange, coordination and planning between institutions and representatives of the various professions, and to promote pubHc and government awareness of the need for conservation of the cultural... 

Formic acid was a product of modest industrial importance until the 1960s when it became available as a by-product of the production of acetic acid by hquid-phase oxidation of hydrocarbons. Since then, first-intent processes have appeared, and world capacity has climbed to around 330,000 t/yr, making this a medium-volume commodity chemical. Formic acid has a variety of industrial uses, including silage preservation, textile finishing, and as a chemical intermediate. 

Solvents. The most widely used solvent is deionized water primarily because it is cheap and readily available. Other solvents include ethanol, propjdene glycol or butylene glycol, sorbitol, and ethoxylated nonionic surfactants. There is a trend in styling products toward alcohol-free formulas. This may have consumer appeal, but limits the formulator to using water-soluble polymers, and requires additional solvents to solubilize the fragrance and higher levels of preservatives. 

A Methylolhydantoins. l,3-Bis(hydroxymethyl)-5,5-dimethyIhydantoia [6440-58-0] is used extensively as a preservative in cosmetic and industrial appHcations, and carries EPA registration for the industrial segment. It is available in soHd and in aqueous solution forms, including low free formaldehyde versions of the latter. A related derivative, l,3-bis(hydroxyethyl)-5,5-dimethyIhydantoia [26850-24-8] is used in the manufacture of high temperature polyesters, polyurethanes, and coatings, offering improved heat resistance, uv stabiUty, flexibiUty, and adhesion. 

Table 13 shows some of the developmental products that have EPA appHcations pending and may be available in the near future. Sea Nine is a variation on the very successflil isothiazolone chemistry. It is claimed to be an improvement over metallic actives used for antifouling paint and wood preservation (46,47). Decylthioethylamine and its water-soluble hydrochloride are claimed to be especially effective at controlling biofilm in cooling water appHcations (48—50). The hydroxymethylpyra2ole shown is also suggested to have properties that are well suited to the protection of aqueous products or emulsions (51,52). 

Pharmaceuticals. A variety of mercury compounds have had pharmaceutical appHcations over the years, eg, mercury-containing diuretics and antiseptics. Whereas some mercury compounds remain available for use as antiseptics such as merbromin [129-16-8] mercuric oxide, and ammoniated mercury [10124-48-8] or as preservatives such as thimerosal [54-64-8] in dmgs and cosmetics, most have been supplanted by more effective substances. A detailed discussion of mercury-containing antiseptics is available (37). Many hospitals use mercury metal to serve as weight for keeping nasogastric tubes in place within the stomach. 

The market for tar-based road binders has declined considerably for a variety of reasons. Less cmde tar is available and the profits from the sales of electrode pitch and wood-preservation creosote or creosote as carbon-black feedstock are higher than those from road tar. In most industrial countries, road constmction in more recent years has been concentrated on high speed motorways. Concrete, petroleum bitumen, or lake asphalt are used in the constmction of these motorways. In the United Kingdom, for example, the use of tar products in road making and maintenance had fallen from 330,000 t in 1960 to 100,000 t in 1975 and is less than 100 t in 1994, mainly based on low temperature pitch which is not suitable for electrode or briquetting binders, but which is perfectly satisfactory as the basis for road binders. 

Shipment and Storage, Specifications. A/-Vinyl-2-pyrrohdinone is available in tank cars and tank trailers and in dmms of various sizes. Shipping containers are normally steel or stainless steel. Tank cars are provided with heating coils to facihtate unloading in cold weather. Rubber, epoxy, and epoxy—phenohc coatings are attacked and must be avoided. Carbon steel has been successfully used for storage tanks, but stainless steel preserves product quahty better. Aluminum and certain phenohc coatings are also satisfactory. 

Disodium Oetaborate Tetrahydrate, Commercially available products, having the approximate composition of a hypothetical disodium octaborate tetrahydrate, have found apphcation in wood (qv) preservatives, fertilizer sprays, insecticides, herbicides, and fire retardants. In many apphcations the large water solubihty of these products is an asset. 

Wood Preservation. The use of chromium compounds ia wood preservation is largely because of the excellent results achieved by chromated copper arsenate (CCA), available ia three modifications under a variety of trade names. The treated wood (qv) is free from bleeding, has an attractive ohve-green color, and is paintable. CCA is widely used, especially ia treating utility poles, bull ding lumber, and wood foundations. About 62% of all the chromic acid produced ia the United States is consumed by the wood preservation industry (77,167) (see Building materials, survey). 

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