Efficacy of preservatives

Baert, L., Debevere, J., and Uyttendaele, M. (2009a). The efficacy of preservation methods to inactivate foodborne viruses. Int. ]. Food Microbiol. 131, 83-94. 

The BP (1988) test for the Efficacy of Preservatives in Pharmaceuticals makes it quite clear that a preservative... 

Rafferty P, Beasley R, Holgate ST. Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuUser solution. Thorax 1988 43(6) 446-50. 

Rafferty P, Beasley R, Holgate S T 1998 Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuliser solution. Thorax 43 446-450 Robinson N, Derksen F, Berney C et al 1993 The ainway response of horses with recurrent airway obstruction (heaves) to aerosol administration of ipratropium bromide. Equine Veterinary Journal 25 299-303 Robinson N, Derksen F, Olszewski M 1996 The... 

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)... 

Balancing advantages and disadvantages the combination of benzalkonium chloride 0.01 % and disodium edetate 0.1 % is the preferred preservative for nasal drops and sprays. Second choice would be methyl parahydroxybenzoate 0.1 %. Detailed information about the efficacy of preservatives in nasal preparations can be found in [47]. 

British Pharmacopoeia (1993) Appendix KV C Efficacy of Antimicrobial Preservation, A191-A192, (and BP 1993, 1995 Addendum Appendix XVIIF, A407). London HMSO. (3.2)... 

Unlike systolic HF, few prospective trials have evaluated the safety and efficacy of various cardiac medications in patients with diastolic HF or preserved ejection fraction. The Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) study demonstrated that angiotensin receptor blockade with candesartan resulted in beneficial effects on HF morbidity in patients with preserved LVEF similar to those seen in depressed LV function.25... 

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. 

Several investigators have published research on incompatibilities of preservatives with rubber closures and other packaging components, particularly polymeric materials [11]. Again, challenging the product with selected microorganisms to measure bacteriostatic or bactericidal activity is necessary, including evaluation of efficacy as a function of time throughout the anticipated shelf life of the product. 

Since the organic mercurials offer an alternative to quaternary ammonium preservatives, and since preservative efficacy of ophthalmic solutions is essential, the choice among these alternatives should be based on a benefit-to-risk analysis as long as a ban is not imposed on the use of these organometallic preservatives. 

Contact lens care products can be divided into three categories cleaners, disinfectants, and lubricants. Improperly cleaned lenses can cause discomfort, irritation, decrease in visual acuity, and giant papillary conjunctivitis (GPC). This latter condition often requires discontinuation of lens wear, at least until the symptoms clear. Deposits can also accumulate preservatives from lens care products and produce toxicity and can act as a matrix for microorganism attachment to the lens [317]. Thus, cleaning with the removal of surface debris, tear components, and contaminating microorganisms is one of the most important steps contributing to the safety and efficacy of successful lens wear [318]. 

Where antioxidants or antimicrobial preservatives are used, the finished product release specification will need to include identification tests and assays for these two types of excipient. The shelf life specification should also include a specification for assay for antimicrobial preservatives. Stability data will be required for both antioxidants and antimicrobial preservatives in the finished product, and in addition the preservative efficacy of the formulated product should be examined over its shelf life and by means of appropriate in-use stability tests. Preservative efficacy data should also be presented at the lower limit of the preservative assay. 

Chemical products should be designed to preserve efficacy of function while reducing toxicity. 

Nonabsorbable antibiotics are appealing because they have fewer systemic side effects and may be safer for children and pregnant women as well as in patients with renal and hepatic dysfunction. One such antibiotic, aztreonam, showed little effect on anaerobic flora in human volunteers, producing most of its effect on the aerobic flora [49, 50], A trial showed efficacy of aztreonam for traveler s diarrhea, where most pathogens are aerobes [51]. While there are no data on rates of AAD for nonabsorbable antibiotics and C. difficile, these would likely be decreased. Given the preservation of the anaerobic flora, another poorly absorbed antibiotic, bicozamycin, has efficacy in traveler s diarrhea with its major effect being on fecal aerobes [52],... 

Sanders et al. [133] found that although quercetin treatment of streptozotocin diabetic rats diminished oxidized glutathione in brain and hepatic glutathione peroxidase activity, this flavonoid enhanced hepatic lipid peroxidation, decreased hepatic glutathione level, and increased renal and cardiac glutathione peroxidase activity. In authors opinion the partial prooxidant effect of quercetin questions the efficacy of quercetin therapy in diabetic patients. (Antioxidant and prooxidant activities of flavonoids are discussed in Chapter 29.) Administration of endothelin antagonist J-104132 to streptozotocin-induced diabetic rats inhibited the enhanced endothelin-1-stimulated superoxide production [134]. Interleukin-10 preserved endothelium-dependent vasorelaxation in streptozotocin-induced diabetic mice probably by reducing superoxide production by xanthine oxidase [135]. 

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. 

Forster, S.C., Hale, M.D. and Williams, G.R. (1997). Efficacy of anhydrides as wood protection chemicals. International Research Group on Wood Preservation, Doc. no. IRGAVP 97-30162. 

Storage and preparation of polyclonal and monoclonal antibodies are very important for successful immunostaining. When a new antibody arrives in a laboratory, special attention should be paid to its storage instructions and optimal temperature. Detailed records of arrival and expiry dates, and whether it needs to be aliquoted to maintain efficacy by avoiding ffeeze-thaw effects, should be kept. Attention to these details will preserve the efficacy of the antibody and its shelf hfe, prevent damaging freeze-thaw cycles, and will make optimization of the immunohistochemical procedures easier, ft is often necessary to aliquot antibodies, especially when storage below 4°C is required. 

Figure 2 Preservative efficacy of Bronopol in a calcium carbonate slurry using the ASTM E723-91 test procedure...

Figure 6 Preservative efficacy of Bronopol and DBDCB alone and in combination in a water-based paint using a multiple challenge test procedure...

In situations where we are trying to show no important loss of efficacy of a test treatment to an active control, it is not possible to be entirely prescriptive about methods for the choice of A. For example, if a new treatment provides an advantage over the existing treatment in terms of safety, the price we are prepared to pay for this in terms of efficacy will clearly depend on the extent of the safety advantage. In these cases it is not appropriate to think in terms of preserving a proportion of the effect of the active control over placebo. 

The main objective of validation of an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose. The procedures presented in this SOP provide basic guidelines for the validation of methods for microbiological assay, estimation of the number of microorganisms, detection of indicators of objectionable microorganisms, validation of preservative efficacy testing, and validation of the sterility testing and endotoxin test (LAL test). 

E. coli is recommended. The microbiological assessment of preservatives is required when preservatives are used in a pharmaceutical product to control microbial bioburden. The test microorganisms and methods for evaluating the efficacy of the preservative in pharmaceutical products are described in the general chapter on preservative effectiveness tests [26]. 

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