Antimicrobial agents Usage in Contact Lens Solution

 Antimicrobial agents

6 basic classes of antimicrobial agents are:
1.    Quaternary ammonium agents and biguanides
2.    Oxidative agent
3.    Chlorine based and chlorine generating systems
4.    Alcohols
5.    Organic mercurial compound
6.    Weak acid

Each can serve as a preservative or disinfectant, depending upon the concentration and the formulation optimization.
In addition, the chelating agent EDTA (Ethylenediaminetetraacetic acid) can appear in combination with them to enhance their antibacterial activity.

1.    Quaternary ammonium agent and biguanides:
In this four carbon group attached to the positively charged nitrogen atom of quaternary ammonium agent.
Most recognized members of the group is benzalkonium chloride (BAK).
Alkyl triethanolammonium chloride (ATEAC) and polymerics, such as polyquaternium-1.
Although chlorhexidine and its polymeric counterpart, PHMB (polyhexamethylene biguanide), are biguanide compounds, they have properties similar to quaternaries.
Benzalkonium chloride (BAK)
In 1935, Benzylkonium chloride was first used as disinfectant and entered the contact lens field in 1947.
It is very potent preservative, it became the agent of choice for rigid contact lens disinfection. Its spectrum of action is wide, even though gram –ve rods can sometimes for resistance cells. For this reason chelating agent EDTA is added, significantly enhancing antimicrobial activity against these resistant cells.
BAK  is incompatible with large negative charged ion (ie. Carboxymethyl cellulose) CMC and anionic surfactant. Concentration mostly used 0.004-0.01%. The negative charged matrix of soft contact lens strongly absorb the +ve charged, small BAK molecules. Subsequent sustained release in to the tear film can cause epithelial cell toxicity.
BAK toxicity has not been observed with PMMA or RGP lenses because it does not concentrate significantly on the lens for this reason BAK is used in RGP lens care product but not hydrophilic lens care product.
Alkyl triethanolammonium chloride (ATEAC)
ATEAC has chemical and antimicrobial characteristics with thimersol to broaden its spectrum and is very potent preservative in its free form. It readily penetrates the soft lens in this state and its subsequent release cause ocular irritation. For this reason it has been formulated only in a semibound form, by adding a controlled amount of surfactant with which the ATEAC complexes. Because ATEAC is bound with surfactant, it is less active than it would be in the free form.
It is available in the form of gluconate, acetate, hydrochloride form.chlorhexidine was the first biguanide used in lens care and it was among the first preservatives used for soft lens solutions.
Chlorhexidine has been implicated as a sensitizing agent, which lead to irritation with chronic use for some patients.
Concentration used for soft contact lens (0.005%) it exerts no significant effect on yeast and fungi.
Chlorhexidine with thimersol (0.001-0.002%) combinations, the two are able to kill or inhibit a broad spectrum of micro-organism like quaternaries, chlorhexidine binds strongly to large negative ions, which can precipitate it.
Polyhexamethylene biguanide (PHMB)
Most common oxidative disinfection agent used in contact lens care product. Two quaternaries – polyquaternarium-1 and water soluble cationic polymer (WSCP) – as well as two polymeric biguanides called PHMB and Polyamino propylbiguanide.
While polymerics can still penetrate a hydrogel, they interact less with the lens than their smaller, more mobile, monomeric counterpart.
They carry over less in to the eye because the lens absorbs smaller amount of the chemical. Polymerics are more active than their monomeric counterpart and hence are used in lower concentration (weight basis). Their large size prevents easy interaction with some micro-organism. They act slowly against some bacteria and are ineffective against mold spores. Action of PHMB is postulated to be interaction with the acidic phospholipids of bacterial membranes.

2.    Peroxides
Two peroxides are currently in use: Hydrogen peroxide and perborate.
Hydrogen peroxide has many features. It acts rapidly and works efficiently against a broad spectrum of microbes. It can be neutralized efficiently, assuring the patient of no carryover in to the eye and minimal residual hydrogen peroxide in the lens.
If the patient fails to fllow the neutralization regimen. Residual peroxide can cause ‘Red eyes, burning and stinging’.
Perborate are used as solution – stable low level peroxide preservatives. They can serve as a preservative without the need for neutralization.

3.    Chlorine based and chlorine generating system
Chlorine based and chlorine generating system include tablet system such as halazone and hypochlorite.
These regimens require the patient to drop a tablet to the sterile storage solution to begin the disinfection process.
Organic materials can neutralize the chlorine that is released by these compounds. This is a drawback regarding antimicrobial efficacy but a plus regarding toxicity because tear protein neutralizes it before toxicity occurs.

4.    Alcohols
Chlorbutanol – it has a broad spectrum of action but as it acts slowly and requires low pH for stability, it seldom serve as the sole preservative in a contact lens solution used at a 0.5% concentration which is very close to its solubility in water.
It has high vapor pressure and may evaporate through the walls of the plastic container, decreasing concentration as well as degrading with time.
Chlorbutanol is currently used only in solutions for PMMA lenses.

Benzyl and Isopropyl alcohols
Benzyl and Isopropyl alcohols served as preservatives. More stable in solution than chlorbutanol.
Benzyl alcohol serves as preservative and disinfectant in hard contact lens. Alcohol interact with soft contact lens, and release in to the tear film, they produce various degree of toxicity and irritation. They also spontaneously convert to aldehyde, which formulator must address because the aldehyde tend to irritate the eye and yellow & harden soft contact lens.

5.    Organic mercurial compound

Thimersol in low concentration served in some soft contact lens solution as a preservative and as a part of a disinfectant system. Thimersol rinses from the lens quickly and efficiently without absorbing, it has been implicated in hypersensitivity reactions. Some patients experience ‘Red eye’ after its usage.

6.    Weak acid

Boric acid – it has a unique property of being isotonic when saturated and served as the universal diluent for ophthalmic drugs. It has preservative activity of boric acid is so minimal. It is no longer used for preservative of contact lens.
Sorbic acid – mainly as a preservatives in bread and dairy products. It has narrow antimicrobial spectrum and is more effective when formulated at a pH of 6.5 or lower.
Alternative for those patients who showed reaction to Thimersol.
Sorbic acid has less antimicrobial activity than Thimersol.

EDTA (Ethylene diamine tetra-acetate) – is a chelating agent (not a preservative) used in ophthalmic product to potentiate preservative efficacy against Gram-negative bacteria. It has a greatest potantiator effect on the genus pseudomonas and also useful against gram –ve enteric bacteria (pseudomonas aeruginosa and pseudomonas alcaligenese).
It acts to remove the cation bridge in the pseudomonas cell wall, where Mg++ and Ca++ cations concentrate.

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