2. LIST OF CONTENT
1) Introduction ……….. 3
2) Ideal properties of preservatives ...…….. 4
3) Classification ...…….. 5
4) Preservatives used in pharmaceutical products...…….. 6
5) Factors affecting preservative efficacy ...…….. 7
6) Preservative efficacy test ...…….. 11
7) References ...…….. 16
8) Questions ...……... 17
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3. ➢ An antimicrobial preservative may be included in a formulation to minimize the risk
of spoilage and kill any contaminant in a non-sterile medicine after manufacturing.
The chemical substances, which are used to preserve pharmaceutical products, food,
and dairy products from decomposition or fermentation by inhibiting or stopping
the growth of microorganisms are known as Antimicrobial Preservatives.
E.g. Methyl paraben, Propyl paraben, Benzaldehyde, and Essential oils.
Antimicrobial Preservatives:
Antimicrobial Preservatives:
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INTRODUCTION
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IDEAL PROPERTIES OF PRESERVATIVES
It should not be irritant and toxic.
01
It should be stable.
02
Preservative should be compatible with other
ingredients used in formulation.
03
It should act as effective antimicrobial agent.
04
It should give optimum action in small concentration.
05
5. PRESERVATIVES
Based on mechanism of
action
Antioxidants
Antimicrobial
agents
Chelating
agents
Based on sources
Natural
preservatives
Artificial
preservatives
1) Butylated hydroxy
anisole (BHA)
2) Butylated hydroxy
Toluene (BHT)
1) Benzoates 1) EDTA salt
2) Citric acid
1) Neem oil
2) Lemon
3) Honey
1) Benzoates
2) Sorbates
3) Nitrates
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CLASSIFICATION OF PRESERVATIVES
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FACTORS AFFECTING PRESERVATIVE EFFICACY
05
04
03
02
01
Interaction with
the formulation
components
Properties of
preservatives
Effect of
containers
Types of
microorganisms
Influence
of pH
8. ➢ Hydrocolloids such as methylcellulose, PVP, alginates, and tragacanth can interact
with preservatives and diminish their activity.
➢ Many emulgents are used in pharmaceutical preparations to produce elegant
applications. The interaction may occur between preservatives and the emulsified oil
phase and with emulgent molecules.
➢ Many tablet additives cause problems in tablet preservation due to interaction with
added preservatives.
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1) Interaction with the formulation components:
1) Interaction with the formulation components:
9. ➢ The distribution of the preservatives must be homogeneous and more solubility in the
bulk phase is preferable in a multiphase system.
➢ Some chemicals such as chlorobutol may hydrolyze on storage if the pH is
unfavorable.
➢ Preservatives may react with substances leached from the container and lose their
antimicrobial activity.
➢ Formulations packed in a glass container can be expected to retain their preservative
content if the closure is airtight.
➢ Preservatives may penetrate through the plastic containers and also react with
closures.
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2) Properties of preservatives:
2) Properties of preservatives:
3) Effect of containers:
3) Effect of containers:
10. ➢ Plant products may contain pathogenic microorganisms from the soil e.g. Clostridium
species, and Bacillus anthracis. These soil microorganisms can cause spoilage of
pharmaceutical products.
➢ Soil organisms are common in dust which may gain access to preparation during
processing or packing.
➢ Adjustment of the pH of the 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 are more active at high pH values.
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5) Influence of pH:
5) Influence of pH:
4) Types of microorganisms:
4) Types of microorganisms:
11. PRESERVATIVE EFFICACY TEST (PET): CHALLENGE TEST
➢ This test is applied to the formulated medicine in its final container to determine
whether it is adequately protected against microbial spoilage.
➢ The test is provided to demonstrate, for multiple dose injectable, nasal, oral, topical,
and ophthalmic products made with aqueous bases or vehicles, the effectiveness of
any added antimicrobial preservatives, the presence of which is declared on the label
of the product concerned.
➢ The tests and standards apply only to the product in the original, unopened container
in which it is supplied by the manufacturer.
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12. ➢ For the initial cultivation of the test microorganisms, use soybean casein digest
medium or any other medium not less nutritive than the said medium.
➢ The intention is to use microorganisms that are likely to arise in the raw material
used in the product and which occur in the manufacturing environments and
represent a particular health hazard if they grew in the product.
➢ A preservative should be active against as wide a range of microorganisms as possible
hence the choice should be of both Gram-positive and Gram-negative bacteria, yeasts
and mold.
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Media:
Media:
Choice of test microorganisms and inoculums preparation:
Choice of test microorganisms and inoculums preparation:
13. ➢ The test microorganisms used in preservative efficacy tests are
1) Staphylococcus aureus ATCC 6538,
2) Pseudomonas aeruginosa ATCC 9027,
3) Escherichia coli ATCC 8739,
4) Candida albicans ATCC 10231
5) Aspergillus niger ATCC 16404
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Procedure:
Procedure:
Inoculate each original product container with one of the
standardized microbial suspension using a ratio equivalent to
0.1 ml of inoculums suspension to 20 ml of product and mix
Determine the number of viable microorganisms by the plate
count method in each inoculums suspension
Incubate the inoculated containers at room temperature
Determine the viable count by the plate count method at 7,14,
21 and 28 days subsequent to inoculation
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Interpretation of results:
Interpretation of results:
➢ The preservative is effective in the product examined if
a) The concentration of viable bacteria is not more than 0.1% of the initial
concentration by the 14th day
b) The concentration of viable yeasts and moulds remain at or below the initial
concentration during the first 14 days
c) The concentration of each test microorganisms remain at or below their
designated level during the remainder of the 28 day test period.
16. REFERENCES
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1) Dr. Imtiyaz Wani, Pharmaceutical Microbiology, PV books, First colour edition,
Page no. 216 to 220
2) Dr. Chandrakant Kokare, Pharmaceutical Microbiology – Principle and Applications,
Eighth edition, Page no. 14.1 to 14.18
3) Dr. Vimal Kumar, Pharmaceutical Microbiology , Technical Publications, Page no.
14-8 to 14-11
17. QUESTIONS
1) Define antimicrobial preservatives. Classify them with suitable example.
2) Discuss in brief about factors affecting preservation efficiency.
3) Write a short note on preservative efficacy test.
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![PRESERVATION OF
PHARMACEUTICAL PRODUCTS
PREPARED BY:
Bhargavi Mistry
[Assistant Professor,
School of Pharmacy, RK University]](https://image.slidesharecdn.com/preservationofpharmaceuticalproduct-230108155513-c7602503/85/Preservation-of-Pharmaceutical-Products-pdf-1-320.jpg)
