A brief knowledge about pharmaceutical preservatives.

1. PRESERVATIVE
PRESERVATIVE ARE HYDROPHOBIC SUBSTANCES, WHICH PROTECT THE FORMULATION AGAINST THE MICROBES.
THEY ARE SIMPLY THE “BODYGAURDS OF PHARMACEUTICAL FORMULATIONS”.
MECHANISM: HOW PRESERVATIVE PROTECT THEM??
ATTACK’S THE
PRESERVATIVE
MICROBE PROTEIN
STRUCTURE

2. Preservative are not meant to
enhance stability of formulation,
but their actual role is to give
exilibity in the use of drug
product.

3. According to USP, in pharmaceutical there are three special names for microorganisms, therefore, instead
of calling microorganism we call them as-
• HARMFUL SUBSTANCE
• OBJECTABLE SUBSTANCE
• OPPORTUNISTIC SUBSTANCE
HARMFUL
• E. Coli
• P. aeruginosa
• S. aureus
OBJECTABLE
• P. multivorans
• S. marcescens
• Klebsiella
• Candida sp.
OPPORTUNISTIC
• P. Putida
• A. anitratus
• P. mirabilis
• P. maltophilia
DEBILITATED means VERY WEAK

4. Preservative’s is mainly used for ORAL PREPARATIONS. Acid
preservative is widely used like p-benzoic acid esters.
For Emulsion- SORBIC ACID is preservative of choice.
SORBIC ACID
P-amino benzoic acid
P-benzoic acid ester

5. Liquid parabens also used very popularly, due to it’s LOW TOXICITY, ODORLESS and THEY DO NOT GET
EASILY DISCOLOUR.
DISADVANTAGE- low aqueous solubility and not effective against Gm(-ve) bacteria.
When they are combined with PHENOXYDIANOL/GERMAN-II substance. They become effective against
Gm(-ve) bacteria.
GERMEN-II (IMIDAZOLIDINYL UREA)
Anti-microbial preservative.
Mainly used in cosmetics
Conc. used- 0.1-0.5%
SYNTHESIS

6. Neutral preservative like VOLATILE ALCOHOLS (benzyl alcohol).
MERCURIALS and QUATERNARY AMMONIUM COMPOUNDS (cationic surfactants), they are excellent
preservatives.
Mercurial- THIMEROSAL, commonly used in vaccines.
IUPAC name- Ethyl(2-mercaptobenzoato-(2-)-O,S) mercurate(1-) sodium
Other name- Mercury((o-carboxyphenyl)thio)ethyl sodium
It can cause mercury poisoning, if used in excess.
OPTIMUM TEMPERATURE at which preservative should be added is 70-75⁰C.

7. DOWICIL 2OO
• Broad spectrum antimicrobial preservative.
• Effective against bacteria, yeast, molds, fungus.
• Conc. Used- 0.02-0.3%
• Stable and cannot be degraded easily.
• Chemical name- cis isomer 1-(3-chloroally)-3,5,7-triaza-1-azoniaadamantane chloride.
• Optimum temp for the usage is 50⁰C.
• Stable at Ph- 4-10
• Discoloring can be prevented by addition of Sodium sulfite to it.
• Used in COSMETICS and SKIN CARE PRODUCTS.

8. PRESERVATIVE EFFICIENCY- Minimum concentration of preservative required to prevent
the growth of microbes.
Techniques used to determine preservative efficiency-
• Determine physicochemical properties of formulation.
• Ultracentrifuge techniques
• Direct dialysis
MICROBIOLOGICAL QUALITY GUIDELINES:
Establish by Cosmetic, Toiletry and Fragrance Association.
• Baby product- 500 microbe per gram/per millilitre (allowed)
• Eye ointments- 500 microbes per gram/ per millilitre (allowed)
• Oral products- 1000 microbes per gram/ per millilitre (allowed)

9. PRESERVATIVE NEUTRALIZING COMPOUNDS
AZOLECTIN- neutralize the Quaternary ammonium compounds(cationic
surfactants)
POLYSORBATE 20 (TWEEN 20)- Neutralize parabens.
AZOLECTIN
TWEEN 20

10. SOME EXAMPLES OF
PRESERVATIVE USED IN
PHARMACEUTICAL SYSTEM

11. BENZALKONIUM CHLORIDE-
Conc. Used- 0.02%
ROA- IM, IV, Nasal, Ophthalmic, Otic
Incompatibility- citrate, methyl cellulose.
BENZITHONIUM CHLORIDE-
Conc. Used- 0.01%
ROA- IM, IV, Ophthalmic, Otic
Incompatibility- Anionic surfactant
BENZOIC ACID-
Conc. Used- 0.1-0.3%
ROA- IM, IV, Oral, rectal, topical, vaginal
Incompatibility- heavy metals, kaolin
BENZYL ALCOHOL-
Conc. Used- 0.75-10%
ROA- Injection, oral, vaginal, topical
Incompatibility- nonionic surfactant, oxidizing agents,
methyl cellulose

12. ETHYL PARABEN-
Conc. Used- 0.001-0.2%
ROA- Topical, oral
Incompatibility- nonionic surfactant, plastic,
silica.
METHYL PARABEN-
Conc. Used- 0.05-0.18%
ROA- IM, IV, SC, Ophthalmic, oral, otic,
rectal, vaginal, topical
Incompatibilities- non-ionic surfactant,
sorbitol
SODIUM BENZOATE-
Conc. Used- 0.1-0.3%
ROA- dermal, IM, IV, oral, rectal, topical
Incompatibilities- gelatin, calcium salts, nonionic
surfactant, cationic surfactant
PHENYL MERCURIC NITRATE-
Conc. Used- 0.001%
ROA- topical, ophthalmic, IM
Incompatibilities- halides, amino acids, rubber

13. CETRIMIDE CREAM-
Chemical name- alkyl trimethyl ammonium
bromide.
Conc. Used- 0.01-0.02%
ROA- topical, ophthalmic
Incompatibilities- ionic and nonionic surfactant
CRESOL-
Conc. Used- 0.1-0.35%
ROA- topical, intradermal, IM, SC
Incompatibilities- nonionic surfactants
PHENOL-
Conc. Used- 0.2-0.5%
ROA- injections
Incompatibilities- albumin, gelatin
THIMEROSAL-
Conc. Used- 0.003-0.012%
ROA- IM, IV, SC, ophthalmic,