Preservation of ophthalmic solutions; a critical evaluation.

(a) bactericidal and fungicidal, (b) compatible with most chemicals used in ophthalmic preparations, (c) non-irritating and non-sensitizing. The most commonly accepted preservative is the mixture of methyl and propylhydroxybenzoates used in the " Solution for Eye-Drops" of the British Pharmaceutical Codex. These hydroxybenzoates, being relatively efficient fungicides, will keep the solutions free from mould growth (Hasler, 1939). In the strength used however, they are not bacteriostatic and will allow the growth of pathogenic bacteria. Chlorbutol (0 5 per cent.) is often used (Adelaide Children's Hospital Pharmacopoeia) although it is not very stable to heat (Murphy and Stoklosa, 1952), and may be somewhat irritating to the eye. The use of phenylmercuric nitrate (1 in 100,000) has also been advocated (Hind and others, 1947), but its bactericidal properties have recently been questioned (Engley, 1950), and even at this low concentration it has many incompatibilities. It is therefore difficult to find a chemical which satisfies all requirements, but many of the desired properties are exhibited by certain quaternary ammonium compounds such as cetrimide B.P., and benzalkonium chloride U.S.P. McPherson and Wood (1949) used 1 in 5,000 benzalkonium chloride as a means of producing " self-sterilizing ophthalmic solutions ". As the quaternary ammonium antiseptics inhibit some organisms in concentrations as low as 1 in 500,000 (Quisno, Gibby, and Foter, 1946), and since high concentrations of these substances may be irritating and incompatible with chemicals used in ophthalmology, it appeared to us that a more dilute solution of these compounds might answer most of the requirements.