Contamination, microbial control with preservatives

Preservatives In addition to those processing controls mentioned above (Section 3.1.4.3), the sterility of a product may be maintained through the addition of antimicrobial preservatives. Preservation against microbial growth is an important aspect of multidose parenteral preparations as well as other formulations that require preservatives to minimize the risk of patient infection upon administration, such as infusion products [52], Aqueous liquid products are prone to microbial contamination because water in combination with excipients derived from natural sources (e.g., polypeptides, carbohydrates) and proteinaceous active ingredients may serve as excellent media for the growth [57], The major criteria for the selection of an appropriate preservative include efficiency against a wide spectrum of micro-... 

Preservatives are intended to offer further protection against environmental microbial contaminants. However, as they are relatively non-specific in their reactivity (see section 7), it is difficult to calculate with any certainty what proportion of preservative added to all but the simplest medicine will be available for inactivating such contamination. Laboratory tests have been devised to challenge the product with an artificial bioburden. Such tests should form part of formulation development and stability trials to ensure that suitable activity is likely to remain throughout the life of the product. They are not normally used in routine manufacturing quality control. 

SLN might be produced aseptically with or without a final sterilization step [40,41], If no sterilization follows the aseptic production, the addition of a preservative is required because the aqueous continuous phase is susceptible to microbial contamination. For biological stabilization of SLN, thiomersal has been used so far [4]. To determine whether the addition of thiomersal to SLN induces cytotoxicity, three different SLN formulations were stabilized with 0.002% (w/w) thiomersal and tested in different concentrations for their tolerability on murine peritoneal macrophages. The same formulations without thiomersal were taken as control. In comparison to the SLN without thiomersal, no increase in cytotoxicity could be detected. 

The pH of shampoos is usually adjusted with a common acid such as citric acid or even mineral acid and buffers such as phosphate, or other inexpensive materials are also used for pH control. Preservation against microbial contamination is necessary and was discussed earlier. 

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