Preservatives/preservation, ophthalmic choice

Microbiologic culture studies are useful fc>r bacterial identification, especially when an ocular infection foils to respond to treatment. Cultures are often obtained from the eyelids, the conjimctiva, expressed material from the lacrimal sac, and the cornea. Because preserved ophthalmic anesthetics have a bacteriostatic effect, cultures should be obtained if possible before anesthetic instillation. In the case of corneal sampling, it is necessary to provide topical anesthesia for patient comfort. The anesthetic of choice is 0.5% proparacaine because it causes the least bacterial growth inhibition. To enhance the bacterial yield, sterile preservative-free anesthetic may be used. Samples obtained may be inoculated directly onto soUd media plates (e.g., blood agar). Amies without charcoal transport medium (e g., BBL CultureSwab Plus) appears to be an acceptable alternative to direct plating and has the added benefit of convenience. 

Although this chapter is directed toward ophthalmic products, it is largely applicable to parenteral and even nonsterile products (solutions, emulsions, and suspensions). The choice of preservative is limited to only a few chemicals that have been found, over the years, to be safe and effective for this purpose. These are benzalkonium chloride, thimerosal, methyl- and propylparaben, phenylethanol, chlorhexidine,... 

Since the organic mercurials offer an alternative to quaternary ammonium preservatives, and since preservative efficacy of ophthalmic solutions is essential, the choice among these alternatives should be based on a benefit-to-risk analysis as long as a ban is not imposed on the use of these organometallic preservatives. 

When formulating aqueous ophthalmic preparations attention should be given to osmolality, pH, solubility, chemical interactions, stability of the active substance, together with viscosity and the choice of a preservative. Sterility is of critical importance and therefore the most appropriate sterilisation method must be chosen. 

The efficacy of a preservative is pH dependent. Therefore the pH value of the ophthalmic solution determines the choice of the preservative. Sorbic acid and benzoic acid present in other dosage forms are active at a pH value lower than 5, and therefore unsuitable in most ophthalmic solutions. 

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