PRESERVATIVES: A Basics


·         Definition: A substance which is added to a preparation to prevent bacterial growth and subsequent spoilage of the preparation.
·         Preservative describes those antimicrobial agents used to protect pharmaceutical preparations.
·         Microbes are growth in non-sterile formulation lead to chemical changes in formulation and spoilage of product hence preservatives are required.
·         Examples: ethanol, alcohol, chlorhexidine, benzoic acid, methyl parabens, ethyl parabens.

·         Antimicrobial preservatives:
o   Emulsions contain water, which will support microbial growth.
o   Microbes produce unpleasant odours, colour changes and gases and may affect the emulsifying agent, possibly causing breakdown of the emulsion.  
o   Examples include arachis oil which supports Aspergillus species and liquid paraffin which supports Penicillium species.
·         Preservation of suspension:
o   All pharmaceutical preparations that contain water are therefore susceptible to microbial growth.
o   Water is the most common source of microbial contamination.
o   Natural polymer such as acacia & tragacanth may be sources of microbes and spores.
·         Preservation of solutions:
o   Most water-containing pharmaceutical solutions will support microbial growth unless this is prevented.
o   Contamination may come from raw materials or be introduced during dispensing.
o   Preservatives may be added to the formulation to reduce or prevent microbial growth. Chloroform is the most widely used in oral preparations.

Mechanism of action:
·         Preservatives interfere with the growth, multiplication and metabolism of micro-organism by following mechanism:
o   Modify membrane permeability of microbes
o   Denaturation of enzymes and other cellular proteins.
o   Oxidize cellular constituents.
o   Hydrolysis

Ideal Properties of preservatives:
·         Exert a wide range of antimicrobial activity at low concentration levels.
·         Maintain activity throughout product manufacture, shelf life and usage.
·         Not affect the quality or performance of product, pack or delivery system.
·         Not adversely affect patient safety or tolerance of the product.
·         It should be effective against a wide range of microorganisms such as bacteria, mold and fungi etc. at room temperature.
·         It should be chemically compatible with other ingredients of the formulation.
·         It should be nontoxic and nonirritant.
·         It should be soluble in aqueous phase when used in emulsions.
·         If the system is biphasic, the partition-coefficient should be in favor of the aqueous phase.
·         It should be odourless, tasteless, and should not impart colour in the formulation.
·         It should be stable and effective over a wide range of pH.
·         It should be thermostable.

Classification of preservatives:
·         Acidic: Phenol, Chlorocresol, O-phenyl phenol, Parahydroxy benzoic acid, Benzoic acid, Boric acid, Sorbic acid
o   Benzoic acid: Used in 0.1% w/v concentration, It is nontoxic unless taken in large quantity, Loss effectiveness above 5.0 pH.
o   Parahydroxy benzoates: Derivatives of benzoic acid, used for syrup and other formulation, Concentration range from 0.05 % to 0.005 %
o   Sorbic Acid: Description-Free-flowing, while, crystalline powder, melt about 1330C, Solubility: 1 gm in 1000 mL water, 10 mL alcohol, 15 mL chloroform, 30 mL ether, or 19 mL propylene glycol, Use: A mold and yeast inhibitor & as a fungistatic agent for foods.
·         Neutral: Chlorobutanol, Benzyl alcohol, Beta- phenyl ethyl alcohol
·         Mercurial: Thiomersal, pheny mercuric acetate and nitrate, Nitromersol
Quaternary Ammonium compounds: Benzalkonium chloride

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