Preservative system

We can expect drastic changes in the food packaging industry. Some will arise from new consumer needs, new or expanded food supplies and products, and new food preservation systems such as aseptic packaging. Others will result from societally based constraints such as safety in health and hazardous use (as in the child safety closure legislation) and consumer protection against fraud, misinformation, or wrongful use where the burden for awareness is no longer on the buyer but on the supplier. Other such constraints will arise from environmental concerns or material scarcities. 

Combinations may also be used to extend the speetrum of a preservative system. Thus, the preservative Germall 115 has an essentially antibacterial activity and very low, if not zero, antifungal aetivity. By combining Germall 115 with parabens, whieh possess antifungal activity, a broader spectrum (antibacterial/antifungal) preservative system is obtained. 

Orth has applied the concepts of the D-value as used in sterilization technology (Chapter 20) to the interpretation of challenge testing. E q)iessing of the rate of microbial inactivation in a preserved system in terms of a D-value enables estimation of the nominal time to aehieve a prescribed proportionate level of kill. Problems arise when trying to prediet the behaviour of very low levels of survivors, and the method has its detractors as well as its advocates. 

Formulators have many factors to consider when selecting an appropriate preservation system for a candidate metalworking fluid. There are three broad areas to consider ... 

It is also important to consider the dose of biocide required to give the desired longevity in-use and compare this to the cost of the preservative. In many metalworking fluids, the preservative system can be the single most expensive component in the formulation. Getting the balance between cost and efficacy is key. 

Biocides are formulated into the concentrates of products at anywhere between 20-25 times the end-use concentration. The preservative system must be soluble in the concentrate which may be a mixture of oil and water. The concentrate may then be stored anywhere between three months to one year. During this period of time, the biocide must remain active if it is to be efficacious when the product is used. There are many components in a metalworking fluid formulation that can deactivate certain types of biocides. For example, the presence of primary amines in many products rapidly deactivate isothiazolinone biocides, making this class of biocides unsuitable for use in the vast majority of metalworking fluid concentrates. 

It is highly recommended that both the efficacy and physicochemical compatibility of the preservation system in the candidate formulation are evaluated using recognised test protocols such as those published by the Institute of Petroleum and ASTM. 

A number of other preservative systems are also widely applied to personal care products and are worthy of mention, some of these being used with increasing frequency, such as bronopol, methyldibromoglutaronitrile and iodopropynyl butylcarbamate, and some used with decreasing frequency, such as formalin and salicylic acid. 

The raw materials used in a particular product may present some challenges to the formulation chemist when selecting the most appropriate preservative. Problem ingredients may act as microbial nutrients, preservative inactivators or preservative adsorbers and careful testing and assessment of the preservative system is necessary in these cases. One notable example of this is the inactivation of parabens esters by certain non-ionic surfactants. 

Cosmetics and toiletries product manufacturers generally aim for 30 months shelf life and hence the product under development must have adequate preservative system to cope with the following -... 

Compatibility - Combination of raw materials is needed to obtain the desired effect from the end product by the user, at the same time minimising the possible reduction in activity of the preservative system ... 

Utilising the usual levels of anti-microbials for cleansing products with normal user instructions of three minutes or longer contact time can achieve positive claims of anti-bacterial for Myavert C based enzyme preservation system without the stinging associated with alcohol. Table 1 gives the plate kill speed data for a face masque where the preservative also becomes a positive attribute. 

This substituted alcohol has been used at 0.5% concentration, but in addition to its weak activity it has several limitations. It is volatile and will lose activity by permeation through a plastic package. It has limited water solubility, can be salted out of solution, and can produce burning and stinging sensations in the eye. It has been recommended primarily for use in combination preservative systems. 

Craig, I.D., Parker, R., Rigby, N.M., Cairns, P., and Ring, S.G. 2001. Maillard reaction kinetics in model preservation systems in the vicinity of the glass transition Experiment and theory. J. Agric. 

All of the above environmental concerns are leading to restrictions being placed upon the use and composition of preservatives used to treat timber. Preservative systems of the future will therefore be selected not simply on the basis of criteria such as efficacy and cost, but also environmental impact, both during service and at the end of product lifetime. This will inevitably have economic implications. 

It is recognized that as wood preservative systems that exhibit broad-spectrum activity are phased out, there will be an increase in the use of systems that are designed to be Tit for purpose . In the area of wood modification, it is well known that some systems perform well in some situations and less well in others. There will need to be a framework of tests that recognize this fact and allow products to be licensed that perform entirely satisfactorily in service, even though they may fail the current tests as they stand at the moment. 

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. 

The release and shelf-life specifications are established based on both the premarketed stability data for the preservative system concentration and the antimicrobial effectiveness test results. 

All preservative systems for both parenteral and nonsterile dosage forms should meet the 3 log reduction at 14 days for bacteria, that is, USP category I requirements. Both EP and BP Antimicrobial Effectiveness Testing would be run only if specially requested by the marketing group. 

Repeat challenges should be limited to the evaluation of preservative systems that cannot be improved because of formulation difficulties and limitations due to the intended site of use and products that may be misused during multiple consumer use. 

Failure of preservative systems to protect liquid products,... 

Results and Discussion. The multiple challenge procedure outlined above represents a relatively severe test for a preservative system. However, systems that perform well under these laboratory conditions should be effective in commercial practice. 

Traegardh, C. Hallstrom, B. Energy Analysis of Selected Food Post-Harvest and Preservation Systems, Irradiators Compared to Conventional Food Preservation Methods. Res. Contract No. 2850/TC, report to the International Atomic Energy Agency, Vienna, 1981. 

In addition to the specific contaminant being objectionable, such contamination would be indicative of a deficient process as well as an inadequate preservative system. For example, the presence of a Pseudomonas putida contaminant could also indicate that P. aeruginosa, a similar source organism, is also present. 

Important specifications for the manufacture of all solutions include assay and microbial limits. Additional important specifications for suspensions include particle size of the suspended drug, viscosity, pH, and in some cases, dissolution. Viscosity can be important, from a processing aspect, to minimize segregation. In addition, viscosity has also been shown to be associated with bioequivalency. pH may also have some meaning regarding effectiveness of preservative systems and may even have an effect on the amount of drug in solution. With regard to dissolution, there are at least three products that have dissolution specifications. These products include pheny-toin suspension, carbamazepine suspension, and sulfamethoxazole and trimethoprim suspension. Particle size is also important, and at this point it would seem that any... 

It is expected that formulation scientists will use this information to benchmark their internal development protocols and reduce the time required to file by adopting formulae that have survived the test of time. Many of us who have worked in the pharmaceutical industry suffer from a fixed paradigm when it comes to selecting formulations Not invented here perhaps is kept in the back of the minds of many seasoned formulations scientists when they prefer certain platforms for development. It is expected that with a quick review of the formulation possibilities that are made available in this book such scientists would benefit from the experience of others. For teachers of formulation sciences this series offers a wealth of information. Whether it is selection of a preservative system or the choice of a disintegrant, the series offers many choices to study and consider. 

In a few cases, preservatives have been already integrated in the formulations. In difficult cases, e.g., antiacid suspensions with a pH more than 7, the preservative system i.e. bacte-ria-free or low-bacteria production, should be the subject of accurate research. 

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