PRESERVATIVES

M.PHARMACY (Ct Institutes) Punjab, India PHARMACEUTICS

PRESERVATIVE

It is a naturally occurring or synthetic substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes.

There are two strategies followed in the manufacture of microbiologically stable, acceptable pharmaceutical preparations.

The first step is to prevent contamination of the product. The second is to formulate the final product so that it is hostile to microorganisms and it is usually done by the addition of preservatives.

NEED FOR PRESERVATIVES

Microbial contamination can cause: Loss of product viscosity Drop in pH Emulsion breakdown Cloudiness and visible growth Loss of colour Malodour Skin problems

MICROBIAL CONTAMINATION SOURCES

Water Air Raw Materials
Low demand gram-negative groups: Pseudomonas, Xanthomonas, Flavobacterium Mould spores: Penicillium, Mucor, Aspergillus Bacterial spores: Bacillus spp. Yeasts Micrococci

Earths
Pigments

Anaerobic spore formers: Clostridium spp

Salmonella Coliforms Actinomyces Salmonella, Coliforms Coliforms, Staphylococci, Sterptococci

Starches
Gums Animal products Personnel

GOOD PRESERVATIVE
Broad-spectrum activity against bacteria, yeast and moulds Cidal rather than static activity Sufficient speed of kill to satisfy accepted challenge test criteria Be stable and effective over the anticipated shelf life of the product Be safe to handle and preferably liquid Be safe at use concentrations Be effective over the pH range of the product Be cost effective

Chemical antimicrobial agents are thus added to all multidose sterile formulations and to aqueous and aqueous-based nonsterile pharmaceuticals.
Their function is to reduce the microbial load to a level, which is safe for the designated use of the product, and to maintain the numbers of viable microorganisms at or below that value for the storage and use life of the product. Different preservatives are enlisted below

BENZOIC ACID
SYNONYM
Benzene carboxylic acid

CATEGORY
SOLUBILITY

Carboxylic acid, aromatic

Soluble in hot water, alcohol, ether, benzene, chloroform, acetone, carbon disulfide, oil of turpentine, carbon tetrachloride, fixed and volatile oils; slightly soluble in petroleum ether, hexane. 0.1% w/v Mixtures, Oral and topical formulations; gums and syrups 2.8 Benzoic acid targets both gram negative and gram positive bacteria and coliforms, especially Escherichia coli, Bacillus cereus, Listeria monocytogenes, Lactobacillus spp., Pseudomonas spp., Candida krusei, Aspergillus niger Sodium benzoate Potassium benzoate Calcium benzoate Ethyl para-hydroxybenzoate Sodium ethyl para-hydroxybenzoate Propyl para-hydroxybenzoate Sodium propyl para-hydroxybenzoate Methyl para-hydroxybenzoate Sodium methyl para-hydroxybenzoate

CONCENTRATION APPLICATION pH SPECTRUM

OTHER AVAILABLE DERIVATIVES

ACID
SYNONYM
2,4-Hexadienoic acid
2-Propenylacrylic acid

CATEGORY SOLUBILITY

Carboxylic acid, aromatic Slightly soluble in water, Freely soluble in ethanol, Acetone, Soluble in ethyl ether, Propylene Glycol

CONCENTRATION APPLICATION

0.35% w/v Oral and topical formulations; gums and syrups

pH
SPECTRUM

3- 5.7
Sorbic acid act primarily against yeasts and molds, Brettanomyces, Candida, Hansenula, Pichia, Saccharomyces, Torulaspora, and Zygosaccharomyces.

OTHER AVAILABLE DERIVATIVES

Sodium sorbate Potassium sorbate Calcium sorbate

THIOMERSAL
SYNONYM
Elicide Merfamin Merthiolate Mercurothiolate Mertorgan Merzonin Thiomersalate

CATEGORY

Organic mercurials

SOLUBILITY

Very soluble in water, Freely soluble in methanol, Insoluble in ether, Benzene 0.004 to 0.01% w/v

CONCENTRATION

APPLICATION

Eye drops; contact lens solutions, vaccines cosmetics, topical medicaments 6.7 - 8.2

pH

SPECTRUM

Broad spectrum of antibacterial activity active against a wide spectrum of nonsporulating Gram-positive

PHENYL MERCURIC ACETATE

SYNONYM
Acetoxyphenylmercury

CATEGORY

Organic mercurials

SOLUBILITY

Soluble in hot ethanol, but poorly soluble in water

CONCENTRATION

0.001 to 0.125% w/v

APPLICATION

Eye drops, Contact lens solutions, Injections

SPECTRUM

Broad spectrum of antibacterial activity

OTHER AVAILABLE DERIVATIVES

Phenylmercuric nitrate

METHYL PARABEN
SYNONYM
Maseptol metaben methylben methyl chemosept methyl parasept Hydroxybenzoate esters

CATEGORY SOLUBILITY

Freely soluble in Diethyl ester, Acetone. Very slightly soluble in Cold water, Hot water, Slightly soluble in carbon tetra chloride, Warm oil, Warm glycerol.Soluble in benzene,oil and fats. 0.1% w/v

CONCENTRATION APPLICATION pH SPECTRUM OTHER AVAILABLE DERIVATIVES

Mixtures, Tablets

2-6

Broad spectrum antibacterial

Methyl paraben sodium

PHENOL
SYNONYM
Carbolic acid Hydroxybenzene Monohydroxybenzene Monophenol oxybenzene phenic acid phenylic acid

CATEGORY

Phenyl alcohol

SOLUBILITY
CONCENTRATION APPLICATION pH SPECTRUM OTHER AVAILABLE DERIVATIVES

Soluble in Water
0.5% w/v Creams 5-6 Broad spectrum antibacterial Orthophenyl phenol Sodium orthophenyl phenol Biphenyl

L
SYNONYM CATEGORY SOLUBILITY CONCENTRATION APPLICATION pH SPECTRUM
Cresylic acid Phenolics

Soluble in Water

0.3% w/v

Creams

3 - 4.8

Inhibits the growth of numerous pathogenic organisms and is a powerful germicide and antiseptic, Rapid activity against grampositive bacteria and fungi

OTHER AVAILABLE DERIVATIVES

Chlorocresol

CHLORHEXIDINE
CATEGORY
Biguanides

SOLUBILITY

Insoluble in Water, Soluble in Alcohal

CONCENTRATION

0.01% w/v

APPLICATION

Solution for hard contact lenses and other opthalmic products

SPECTRUM

Mainly active in cationic form against grampositive bacteria, limited antifungal activity

OTHER AVAILABLE DERIVATIVES

Chlorhexidine acetate

SULPHUR DIOXIDE
SYNONYM SOLUBILITY CONCENTRATION APPLICATION pH SPECTRUM OTHER AVAILABLE DERIVATIVES
Sulphur superoxide Soluble in water 400 parts/106
Vitamins

3- 6.7

Antibacterial Antifungal

Sodium sulphite Sodium hydrogen sulphite Sodium metabisulphite Potassium metabisulphite Calcium sulphite Calcium hydrogen sulphite Potassium hydrogen sulphite

CETRIMIDE
SYNONYM
Tetradecyl trimethyl ammonium bromide

CATEGORY

Quaternary ammonium compounds

SOLUBILITY

Soluble in water

CONCENTRATION

0.01% w/v

APPLICATION

Eye drops; surgical creams; ointments

SPECTRUM

Narrow spectrum (gram-positive bacteria) of activity

CHLORPHENESIN
SYNONYM
Cosvat Maolate Musil Glycerol ether Freely soluble in Acetone, Chloroform, Benzene; Soluble in Alcohal, Ether; Slightly soluble in Fixed oil ,Water

CATEGORY SOLUBILITY

CONCENTRATION APPLICATION pH SPECTRUM

0.0125 -0.04% w/v Cosmetics 4.5 - 8 Antifungal and antibacterial characteristics Escheria Coli Pseudomonas aeruginosa Staphylococcus aureus Candida albicans Aspergillus Niger

BISPHENOL
SYNONYM
Diane Diphenylolpropane Phenolics Very soluble in Alcohal, Very slightly soluble in Water, Insoluble in Oil 0.03% w/v Creams 2 - 12 Rapid activity against gram-positive bacteria and fungi Bisphenol A Bisphenol AP Bisphenol AF Bisphenol B Bisphenol BP Bisphenol C Bisphenol E Bisphenol F

CATEGORY SOLUBILITY

CONCENTRATION APPLICATION pH SPECTRUM

OTHER AVAILABLE DERIVATIVES

BENZALKONIUM CHLORIDE
SYNONYM
Alkylbenzyl-dimethylammonium chloride; Alkylbenzyldimethyl.

CATEGORY SOLUBILITY

Quaternary ammonium compounds

Soluble in both water and alcohol. Soluble in acetone. Very slightly soluble in diethyl ether.

CONCENTRATION APPLICATION pH SPECTRUM

0.1 to 0.3%% w/v

Eye drops; surgical creams; ointments

4 - 10

Narrow spectrum (gram-positive bacteria) of activity

THANKS