Preservatives concentrations

Dispersions to be added to latex must have good storage stabiHty and be compatible with the latex the pH of each should be similar to that of the latex, eg, pH 8.5—11 for ammonia-preserved latex and pH 3.5 for cationic-preserved concentrates. Addition of low pH materials to high pH latex or vice versa generally results in mutual precipitation and coagulation of the suspended mbber particles. 

Infection induced by contaminated 22 Effect of preservative concentration,... 

Effect of preservative concentration, temperature and size of inoculum... 

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. 

The selection of the preservative system for multiuse new products is the responsibility of the R D formulation group. Typical shelf specifications are 80 to 120% of label specifications. The appropriate preservative system for the particular formulation should be demonstrated to be effective by microbial challenge to at least 75% and preferably 50% of the target concentration. It is recommended that during development the product be formulated with preservative concentrations of 100, 75, and 50% of the labeled amount and be subjected to antimicrobial effectiveness testing to determine the lowest effective preservative concentration. 

Another important component of most vaccine formulations is a suitable preservative. The three most commonly used preservatives in available vaccines are phenol, 2-phenoxyethanol, and ethyl mercurithiosalicylate (thimerosal). Thimerosal, in particular, is used in multidose vials as an antimicrobial preservative. Concerns about the presence of mercury in thimerosal (25 pg/dose) has led to FDA stopping the use of this preservative in all vaccines by an amendment to the FDA Modernization Act of 1997. By 2001, thimerosal was removed from most childhood vaccines as a precautionary measure. The sources of all of the preservatives for vaccines are the same suppliers that supply preservatives for the parenteral dosage forms (J. T. Baker, Aldrich, Spectrum, etc. from U.S.A.). Table 2 lists some of the preservative concentrations in common vaccines. 

Acidic preservatives are the most widely used for oral preparations, such as the p-Hydroxybenzoic acid esters and salts of benzoic acid. These are adequately soluble in aqueous systems and possess both antifungal and antibacterial properties. Methyl and propyl p-hydroxybenzoic acid are often used together in a 10 1 ratio. Concomitant use of multiple esters makes possible a higher total preservative concentration owing to the independent solubilities of each and, according to some researchers, maximizes the antimicrobial effect. 

Table 2 Some examples of preservative concentration exponents...

Nylon strongly adsorbs phenols and sorbic acid by covalent linkage. The degree of interaction depends on the pH, nature of the solvent, temperature, contact time, surface area, preservative concentration, and thickness of the nylon. 

Benzyl alcohol is an antimicrobial preservative used in cosmetics, foods, and a wide range of pharmaceutical formulations, including oral and parenteral preparations, at concentrations up to 2.0% v/v. In cosmetics, concentrations up to 3.0% v/v may be used as a preservative. Concentrations of 5% v/v or more are employed as a solubilizer, while a 10% v/v solution is used as a disinfectant. 

Chemburkar PB, Joslin RS. Effect of flavoring oils on preservative concentrations in oral liquid dosage forms. ] Pharm Sci 1975 64 414-417. 

SO2 (50-100 ppm) is added to expressed grape juice to control unwanted moulds, bacteria and yeasts depending upon the condition of the grapes. It is also used in treatment of soft-fruits in order to extend the time available for jam manufacture. Sausage and meat products are treated with SO2 to extend their shelf life under refrigerated conditions. Soft drinks may contain 10 ppm (Continental Europe) -70 ppm (UK), some of which may originate from preserved concentrated fruit juices. 

Organic Acids and Food Preservation concentrates on safe and effective techniques for applying organic acids to prevent bacterial growth and promote food preservation and enhancement. Despite the wide range of potentially useful antimicrobials, relatively few are suitable in practice—and this invaluable hands-on guide explains why. 

Sterile vaginal solutions are packaged in a single-dose container that can be sterilised, for instance glass (preferably class I, eventually class II) or plastic (polypropylene). Preserved concentrates, intended to be diluted before use, are usually packaged in a container of glass (class III) or plastic (polypropylene, polyethylene) meant for multiple dosing. 

Torres, J.A., Motoki, M. and Karel, M. (1985) Microbial stabilization of intermediate moisture food surfaces 1. Control of surface preservative concentration. J. Food Proc. Pres. 9, 75-92. 

As a result of frequently varying use-concentrations of a coolant, depending e.g. on the work process, a standard preservative concentration cannot ensure microbiological effectiveness over the entire concentration range. In one case the concentration for adequate effectiveness is too low, in another case too high. The use of prepreserved coolants is therefore possible only to a very limited extent, e.g. in individual machines. 

The information to be recorded should include microorganism count, rough differentiation of the flora into bacteria and fungi, preservative, preservative concentration, and amounts of preservative added. 

It is clear from this that handling and using such substances can involve some risks. In particular, harm can occur as a result of contact with skin and mucous membranes. It is vital that the stipulated protective measures-especially when handling the preservative concentrates - are adhered to. 

Microbial attack of vinyl chloride has been shown to occur (Nelson, Y.M. and Jewell, W.J., 1993) and still further it is known that vinyl acetate breaks down to give acetaldehyde and acetate (Nieder, M., Sunarko, B. and Meyer, O., 1990), both metabolities being microbial nutrients at the concentrations found in typical polymer dispersions, where free vinyl acetate concentrations can be in the order of 0.1%. At higher levels, as may have been found some years ago, acetaldehyde would have been present at preservative concentrations. 

Partition coefficient. Lipophilic preservatives tend to accumulate in the lipid phase of a formulation. This phenomenon is particularly important when planing preservative systems for emulsions, where the partition coefficient, as the ratio of preservative concentrations in the oil and water phases respectively, is a significant index of how they partition in emulsions. Adding alcohol to an aqueous milieu can shift the distribution coefficient in favour of the aqueous phase. In contrast, non-ionic surfactants tend to shift the partition coefficient in favour of the oil phase, resulting in a reduction of preservative efficacy in the water phase (WallhauBer, 1984). 

The above tests are all labor-intensive and time-intensive. Orth [19] has developed a test which may predict the behavior of preservatives in only 48 h. This test is based on measurements of the kinetics of cell death. In this test, the decimal reduction time (D value) [i.e., the time required for one log (90%) reduction in the bacterial population] is obtained by linear regression for different preservative concentrations. This gives a rate of killing of specific organisms and also allows comparisons between the effectiveness of different antimicrobials. Criteria of preservative acceptance based on the D value are discussed in detail elsewhere [20]. 

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