Def :- The word preservative in the broad sense indicate A substance used to preserve

They may be Anti-microbial agents Anti-oxidants

Anti-microbial agents
These are substances added to pharmaceutical formulations to prevent or to inhibit the growth of micro-organisms in the preparation.

Why ? what is the necessity ?

To store formulations for long periods To prevent the microbial degradation.

Example :

1. Emulsions and suspensions Contain water + carbohydrates (natural emulsifying and suspending agents)

Provide good medium for multiplication of bacteria and moulds (ex: Pseudomonas, E.coli, Salmonella, Staphylococcus)
2. Multi-dose parenterals.

Points to be considered in selection of preservatives

Site of use internal, external or ophthalmic.

Choice of preservatives(selection criteria)

It must possess the general criteria of low toxicity or non-toxic. Stability to heat and storage. Chemical compatibility. Reasonable cost. Acceptable taste, odour and colour. Effective against wide range of microorganisms. In case of ophthalmics, it should be nonirritating.

Certain hydro-alcoholic and alcoholic preparations do not require addition of preservatives. Ex : Elixirs, Spirits and Tinctures self Preservating. In general, alcohol content of 15% by weight in acid solutions and 18% by weight in alkaline solutions is sufficient to prevent microbial growth.

Mode of actions
They interfere with growth, multiplication or metabolism of M.Os
Alter cell membrane permeability causing leakage of cell constituents(partial or complete lysis) Coagulation of cytoplasmic constituents(protein pptn) Inhibit cellular metabolism by interfering with enzyme systems (oxidation of cellular constituents or hydrolysis)

Factors influencing preservative activity :Surfactants. pH. Phase ratio. Degree of aeration during preparation. Presence of flavors and perfumes.

Generally, no single preservative possess all the qualities; Hence their different combinations are used.

Classification
Type
Acids and acid derivatives

Example
Benzoic acid(0.1-0.2%) Sorbic acid and salts(0.05-0.2%) Propionic acid and salts Chloro-butanol Phenoxy-2-Ethanol Formaldehyde Glutaraldehyde Phenol (0.2-0.5%) Cresol (0.05-0.1%) Chloro-thymol P-chloro-meta-xylenol Methyl-P-hydroxy benzoate (0.1-0.2%) Propyl-P-hydroxy benzoate (0.1-0.2%) Chlor hexidine and salts Benzethonium Chloride Benzalkonium Chloride (0.004-0.02%) Cetyl tri methyl ammonium bromide Phenyl mercuric acetate Phenyl mercuric nitrate (0.002-0.005%) Sodium ethyl mercuri-thio-salicylate Imidizolidinyl urea compounds 2,4,4 tri chloro, 2-hydroxy, di phenyl ether

Characteristics and Utility

Anti-Fungal Eye preparations Synergist Broad spectrum

Alcohols Aldehydes Phenolics

Quaternary ammonium compounds

Broad spectrum

Mercurials

Broad spectrum Synergist Primarily against gram +ve

Miscellaneous

Interactions
Phenolic preservatives preservative in-activation by surfactants It rests on concept that, part of preservative is unavailable for activity by virtue of incorporation into surfactant micelles.
Compound Gelatin Preservative MP MP MP MP %free 92 91 84 78 %bound 8 9 16 22 Preservative PP PP PP PP %free 89 87 81 64 %bound 11 13 19 36

Methyl cellulose PEG 4000

PVP

Various alcohols activate P-hydroxy benzoate esters in presence of non-ionics

Evaluation:No.of viable M.Os Vs Time profile. Quantity of preservative compounds Vs Time profile.

References:RPS Lachmann Mithal Bajaj and Gupta

THANK YOU

R. Venkatesh