DIFFERENT PRESERVATIVES USED IN PHARMACEUTICAL

INDUSTRIES

SYNOPSIS
FOR
M.Sc. (Chemistry)

Submitted by: Under the Guidance of:

Harshika Dr. Joginder Singh
11207835 Associate Professor
M.Sc. (Chemistry) Chemitry Department,
M.M.E.C., M.M.D.U. Mullana,
Ambala
CONTENTS
Sr. No. Contents Slide No.
1 Introduction 3
2 Classification of Preservatives 4-6
3 Ideal Properties of Preservatives 7
4 Mechanism of Action 8
5 Performance Requirement 9
6 Significance of Concentration and Requirement 10
7 Factors Affecting Preservative Efficiancy 11
8 Interaction with formulation components 12
9 Effect of containers 13
10 Types of microorganisms 14
11 Influence of pH 14
12 Different Pharmaceutical Preservative 15-21
13 Conclusion 22
14 Reference
 PHARMACEUTICAL PRESERVATIVES

Preservatives are substances added to various pharmaceutical dosage

forms and cosmetic preparations to prevent or inhibit microbial
growth.

An ideal preservative would be effective at low concentrations against

all possible micro-organism, be nontoxic and compatible with other
constituent of the preparation and be stable for the shelf-life of the
preparation.
Classification of Preservatives
Preservatives are classified on variety of the basis and some of these are
as follows

A. CLASSIFICATION BASED ON MECHANISM OF ACTION

1. Antioxidants:
The agent which prevent oxidation of Active
pharmaceutical ingredient which otherwise
undergo degradation due to oxidation as they
are sensitive to oxygen.
Ex. Vitamin E, Vitamin C, Butylated hydroxy
anisole ( BHA), Butylated hydroxy toluene (BHT).
2. Antimicrobial agents:
The agent which active against gram positive &
gram negative microorganism which causes
degradation of pharmaceutical preparation which
are active in small inclusion level.
Ex. Benzoates , Sodium benzoate, Sorbates

3. Chelating agents:
The agents which form the complex with
pharmaceutical ingredient and prevent the
degradation of pharmaceutical formulation.
Ex. Disodium, ethylenediamine tetraacetic acid
(EDTA), Polyphosphates , Citric acid
B. CLASSIFICATION BASED ON SOURCE
1. Natural Preservatives:
These preservatives are obtained by natural sources
that are plant, mineral and animal sources etc.
Ex. Neem Oil, Salt (sodium chloride), Lemon,
Honey.

2. Artificial Preservatives:
These preservative are man made by chemical
synthesis and active against various microorganisms
in small concentration.
Ex. Benzoates, Sodium benzoate, Sorbates,
propionates, nitrites.
Ideal properties of Preservatives

• It should not be irritant.

• It should not be toxic.
• It should be physically and chemically stable.
• It should be compatible with other ingredients used in formulation.
• It should be act as good antimicrobial agent and should exert wide spectrum
of activity.
• It should act in small concentration i.e. it must be potent.
• It should maintain activity throughout product manufacturing, shelf life and
usage.
Mechanism of Action
• Natural substances such as salt, sugar, vinegar, and
diatomaceous earth are also used as traditional preservatives.

• Certain processes such as freezing, pickling, smoking and

salting can also be used to preserve food.

• Another group of preservatives targets enzymes in

pharmaceutical products that continue to metabolize.
Performance Requirements

Antimicrobial Activity • Active Against Microbes at Low Concentration

• Should Be Soluble To Reach Minimum Inhibitory

Aqueous Solubility
Concentration

Stability Properties • Stable During and at the End of Manufacturing

• Remain in Continuous Phase in Multiphase

Partitioning Behaviour
Products

• Odour and Acceptable Taste During

Organoleptic Properties Administration of the product
SIGNIFICANCE OF CONCENTRATION AND
TEMPERATURE

Concentration Temperature

Activity changes
Change in conc.
with
will change the
temperature,
efficacy
according to Q10

Ex. Phenol Ex. Phenol

Chlorohexidene Ethanol
FACTORS AFFECTING PRESERVATIVE
EFFICACY
1.Interaction with formulation components
2. Effect of containers
3. Types of micro-organisms
4. Influence of pH
 Interaction with formulation
components

• Hydrocolloids such as methylcellulose, alginates, tragacanth can interacts with

preservatives and diminish their activity.
• Many emulgents are used in pharmaceutical preparations to produce elegant
applications. Interaction may occur between preservatives and emulsified oil
phase and with emulgent molecules.
• Nature of oil, oil water ratio, type of concentration of emulgent, influence the
concentration of preservatives needed to protect the system.
• Many tablet additives cause problems in tablet preservations due to their
interaction with added preservatives.
Effect of containers

• Formulations packed in glass containers can be expected to retain their

preservative content if closure is airtight.
• Preservatives may penetrate through the plastic container and interacts with
it.
• Rubber also reacts with many preservatives but is still used for closures.
• Containers or closures may cause contamination of pathogens.
Types of microorganisms
• Plants products may contain pathogenic microorganisms from the soil.
Ex. Clostridium species, Bacillus anthracis. These soil microorganisms
can cause spoilage of pharmaceutical products.
• Many products prepared from animal sources may contain pathogens
like Salmonella typhi.
• Spores of tetanus and gas gangrene have been isolated from gelatin.

Influence of pH
• Adjustment of the pH of solution may affect the chemical stability and the activity
of the preservative.
• The majority of preservatives are less dependent upon pH, although cationic
active quaternary ammonium compounds (Benzalkoniumchloride, Etilbencil
chloride, Alkyl Dimethyl Ethyl Benzyl Ammonium and Dioctyl Dimethyl Ammonium
Chloride) are more active at high pH values.
Different Pharmaceutical Preservatives

BENZOIC ACID
❑ It inhibits the growth of microbes
including mould, yeast and some
bacteria.
❑ Used as antiseptic also
❑ It is used as a food preservative.
METHYLPARABENS

❑ It is a white crystalline powder,

characteristic odour, freely soluble in
water and alcohol.
❑ It is used as antiseptic and preservative
in various pharmaceutical preparations.
❑ It is also used in cosmetic preparation
susceptible to decomposition.
SODIUM BENZOATE

❑ It is a white crystalline solid, soluble in

water and alcohol.
❑ It is used extensively as food and
pharmaceutical preservatives.
❑ It is not a bactericidal, only a
bacteriostatic agent along with
fungistatic activity.
ALPHA TOCOPHEROL

❑ It is primarily recognized as a source of

vitamin E
❑ It exhibits antioxidant properties, the beta,
delta, and gamma tocopherols are
considered to be more effective as
antioxidants.
❑ It is an excellent solvent for many poorly
soluble drugs of wide spread regulatory
acceptability
ASCORBIC ACID

❑ It is useful as a stabilizing agent in

mixed micelles containing tetrazepam.
❑ Occurs as a white to light-yellow-
colored, non hygroscopic and odorless.
❑ It gradually darkens in color upon
exposure to light.
BUTYLATED HYDROXYTOULENE

❑ It delays oxidative rancidity of fats and

oils, and prevents loss of activity of oil-
soluble vitamins.
❑ It may be found in pharmaceutical gels,
creams and liquid or gelatin capsules,
tablets and other pharmaceutical dosage
forms.
❑ It helps to prevent the formation of free
radicals and oxidation.
HEXACHLOROPHENE

❑ It is a chlorinated bisphenol antiseptic

used as a surgical scrub and skin
cleanser.
❑ It is an ingredient of various
preparations used for skin disorders.
❑ It may also be used to control an
outbreak of gram-positive infection.
CONCLUSION

❑ Synthetic preservatives which are used in preserving foods,

cosmetics, etc. natural preservatives has fewer side effects.
❑ Natural preservatives not only reduce the bacterial growth but
increases the shelf life of the ingredient in which it is added.
❑ They are also good but research has reported that they cause
many health problems as almost all are carcinogenic in nature.
❑ Hence, it may better to use natural preservatives instead of
synthetic one, as it provides us so many good effects.
REFERENCE

1. Chiori CO, Ghobashy AA. A potentiating effect of EDTA on the bactericidal activity of
lower concentrations of ethanol. Int J Pharm ;1983.
2. Clarke CD, Armstrong NA; Influence of pH on the adsorption of benzoic acid by
kaolin; Pharm J; 1972; 62(3); 44-45.
3. Prickett PS, Murray HL, Mercer NH, Potentiation of preservatives (parabens) in
pharmaceutical formulations by low concentrations of propylene glycol. J Pharm Sci;
1961.
4. Saleh SI, P. Wehrle, A. Stamm, Improvement of lubrication capacity of sodium
benzoate: effects of milling and spray drying. Int J Pharm 1988.
5. PB Nielsena, A Mullertzb, T Norlinga, HG Kristensen, The effect of a-tocopherol on the
in vitro solubilization of lipophilic drugs; Int J Pharm; 2001.
6. Hajratwala BR. Stability of ascorbic acid. STP Pharma; 1985.
7. FAO/WHO. Toxicological evaluation of certain food additives with are view of
general principles and of specifications. Seventeenth report of the joint FAO/WHO
expert committee on food additives. World Health Organization Tech Rep Ser 1974.
8. FAO/WHO. Evaluation of certain food additives and contaminants. Twenty-seventh
report of the joint FAO/WHO expert committee on food additives. World Health
Organization Tech Rep Ser ss.