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PRESERVATIVES
• The preservatives are added in pharmaceutical preparation to prevent contamination, deterioration, and
spoilage by bacteria and fungi (Microorganism).
• No single preservative exists that satisfies all of these requirements for all formulations. Frequently, a
combination of two or more preservatives are needed to achieve the desired antimicrobial effect.
❖ Classification of preservatives

A. On the basis of Mechanism of action

1. Antimicrobial agents
• These agents active against gram positive & gram negative micro-organism which causes
degradation of pharmaceutical preparation.
• These agents act against microorganisms by affecting the various cellular portions of microbial
cell and thereby inhibiting their growth.
• Cell wall, cytoplasmic membrane and cytoplasm are such portions of microbial cell wall that are
mostly targeted by the preservatives.
• The antimicrobial agents that have been used as preservatives can be classified into four major
groups: acidic, neutral, mercurial, and quaternary ammonium compounds.

Type of Antimicrobial agent Example with Concentration

Phenol: 0.2–0.5
Chlorocresol: 0.05–0.1
o-phenyl phenol: 0.005–0.01
Acidic
Alkyl esters of parahydroxy-benzoic acid: 0.001–0.2
Mostly used for Oral Preparation
Benzoic acid and its salts: 0.1–0.3
Boric acid and its salts: 0.5–1.0
Sorbic acid and its salts
Chlorbutanol: 0.5
Neutral Benzyl alcohol: 1.0
o-phenylethyl alcohol: 0.2–1.0
Thimerosal 0.001–0.1
Mercurial
Phenylmercuric acetate and nitrate 0.002–0.005
Benzalkonium chloride 0.004–0.02
Quaternary ammonium compounds
Cetylpyridinium chloride 0.01–0.02
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Note:
Acidic Antimicrobial agent:
• Phenols: little used in oral pharmaceuticals, owing to their characteristic odor and instability when
exposed to oxygen.
• p-hydroxybenzoic acid esters and the salts of benzoic and sorbic acid
→ have both antifungal and antibacterial properties
→ have aqueous solubility
→ Mostly used for oral preparation
• The remaining three classes of preservatives (i.e. neutral, mercurial, and quaternary ammonium
compounds) have been widely used in ophthalmic, nasal, and parenteral preparation).
❖ There are three term that are used to describe microbial organisms associated with pharmaceutical and
cosmetic products:
i) Harmful
ii) Objectionable
iii) Opportunistic
i) Harmful
• The term “harmful” to refer to microbial organisms or their toxins that are responsible for human
disease or infection.
• Examples of organisms that must not be present in a product are
o Salmonella species
o Escherichia coli
o Psudomonas aeruginosa
o Staphylococcus aureus
ii) Objectionable
• An “objectionable” organism can cause disease, or its presence may interrupt the function of the
drug or lead to the deterioration of the product.
• Example: P. putida, P. multivorans, P.maltophilia, Proteus mirabilis, Serratia marcescens, Klebsiella
sp., Acinetobacter anitratus (Bacterium anitratum), and Candida sp.
iii) Opportunistic
• Organisms are defined as “opportunistic” pathogens if they produce disease or infection under
special environmental situations, as in the new born or the debilitated person.
2. Antioxidant
• They are self reducing agents that oxidize themselves and prevent oxidation of the components that are
sensitive to oxygen.
• There are three main types of antioxidants:
i) True Antioxidants (water insoluble)
• They act by a chain-termination mechanism by reacting with free radicals, e.g. Butylated hydroxy
anisole (BHA), Butylated hydroxy toluene(BHT)
ii) Reducing Agents (water soluble)
• They have a lower redox potential than the drug and get preferentially oxidized, e.g. ascorbic acid.
Thus, they can be consumed during the shelf-life of the product.
iii) Antioxidant Synergists (chelating agents)
• These enhance the effect of antioxidants, e.g. EDTA (ethylenediamine tetraacetic acid), tetraacetic
acid derivatives and salts, dihydroxyethyl glycine, citric acid, and tartaric acid.
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Antioxidant Example
Sodium sulfite
Sodium metabisulfite
Sodium bisulfite
Sodium thiosulfate
Sodium formaldehyde sulfoxylate
Sulfur dioxide
Antioxidants commonly used for aqueous systems/water soluble
Ascorbic acid
Isoascorbic acid
Thioglycerol
Thioglycolic acid
Cysteine hydrochloride
Acetylcysteine
Butylated hydroxy toluene (BHT)
Butylated hydroxy anisole (BHA)
Ascorbyl palmitate
Hydroquinone
Antioxidants commonly used for oil systems/Water insoluble
Propyl gallate
α-tocopherol
Nordihydroguaiaretic acid
Lecithin

3. Chelating Agents
• The effectiveness of antioxidants can be enhanced through the use of synergists such as chelating agents.
• Chelating agents tend to form complexes with the trace amounts of heavy metal ions inactivating their
catalytic activity in the oxidation of medicaments.
• Examples of some chelating agents are ethylenediamine tetraacetic acid derivatives and salts,
dihydroxyethyl glycine, citric acid, and tartaric acid.

B. On the basis on source

1. Natural Preservatives
• These drugs are obtained by natural sources that is plant, mineral sources, animal etc.
• Eg. Neem Oil; Salt (sodium chloride); Lemon; Honey
2. Artificial Preservatives
• These preservative are man made by chemical synthesis active against by various micro-organisms in
small concentration.
• Eg- Benzoates, Sodium benzoate Sorbates, propionates, nitrites