preservatives PHT 434

prreservatives Preservative: Is a substance or mixture of substances added to a product formulation to prevent the growth of, or to destroy of , microorganisms introduced accidently once the container is opened for use.

Why using preservatives? They must be added in adequate concentration at the time of use to prevent the multiplication of microorganisms inadvertently introduced into the preparation while withdrawing a portion of the contents with hypodermic needle and syringe.

Why using preservatives? The possibility that microorganisms might contaminate medicines during manufacture, storage or use must be addressed to ensure the continued stability and safety of the product. The complex chemical and physicochemical nature of many formulations is often found to be conducive to the survival and even multiplication of such contaminants, unless specific precautions are taken to prevent it.

How mush preservatives can be used? Because antimicrobial agents may have inherent toxicity for patient, the USP prescribes maximum volume and concentration limited for those that are used commonly in a parental product.

Examples of parenteral preservatives Conc. Antimicrobial agent 0.002% Phenylmercuric nitrate# 0.01% Thimerosal Benzethonium chloride Benzalkonium chloride 0.5% *Phenyl Cresol chlorobutanol 0.18% 0.02% In combination Methyl p-hydroxybenzoate & Propyl p-hydroxybenzoate (parabens) * 2% *Benzyl alcohol # not used because mercury toxicity, * Most widely used

How to select preservatives? Particular agents may be effective in one formulation and ineffective in another. so, Compatibility with all other components of formula must be evaluated. Activity must be evaluated in the total formula. e.g. Binding and inactivation of parabens by macromolecules such as polysorbate 80.

Preservatives uses Preservatives are used with: Multidose parenteral (insulin) Single dose, small volume parenteral for which the sterilization was not the last step of production.

Preservatives not used with Single dose containers and pharmacy bulk packs that do not contain antimicrobial agents are expected to be used promptly after opening or to be discarded. Large-volume , single dose containers Preservation is prohibited as the amount of preservative will be high.

Protein pharmaceutical Protein pharmaceutical are preferred to be available as multiple dose because of: Cost frequency of use e.g. Human insulin, human growth hormone, vaccines However, several proteins are reactive with preservative (e.g. interleukins) and, therefore, are only available as single dosage form units.

Criteria may be useful in preservative selection The agent should have a broad spectrum and be active against Gm+ve and Gm-ve organism as well as fungi. The agent should exert a rapid bactericidal activity. The agent should be stable over a wide range of condition including autoclaving temperatures and pH range. Compatibility should be established with other component of the preparation and with package systems. Lack of toxicity and irritation should be established with a reasonable margin of safety.

Preservative are used for topical ophthalmic products packaged in multiple dose container unless the formation itself is self-preservative, as in the case with some antimicrobial products like the ophthalmic solution Vigamox.