386 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS overshadowed in pharmacy curricula by consideration of tonicity, and the attendant calculations now shown to be largely unnecessary. The time would seem appropriate, and even overdue, to adjust long held ideas relating to ophthalmic formulations. (Received: 77th September 7964) (24) (25) (26) (27) (28) (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) REFERENCES (1) Riegelman, S. and Vaughan, D. G. J. Am. Pharrn. Assoc. Pract. Pharrn. Ed. 19 474 Et seq. In three parts. (year). (2) Rogers, K. B. J. appl. Bact. 23 533 (1960). (3) Gould, J. C. in Infection in hospitals. Epidemiology and control. 119 (1963) (Blackwell, Oxford). (4) Brown, M. R. W., Foster, J. H. S., Norton, D. A. and Richards, R. M. E. Pharrn. J. 192 S (1964). (5) Crompton, D. O., Murchland, J. B. and Anderson, K. F. Lancet 1391 (20 June 1964). (6) Crompton, D. O. Austral. y. Pharm. (30 October 1962). (7) Henkind, P. and Fedukowicz, H. Arch. Ophthalrnol. 70 791 (1963). (8) Rhodes, M. E. Ph.D. Thesis (1957) (University of Reading). (9) Hugo, W. B. and Foster, J. H. S. y. Pharrn. Pharmacol. 16 209 (1964). (10) Duke-Elder, Sir Stewart in Parsons' Diseases of the Eye 13th Edn. (1959) (Churchill, London). (11) Riegelman, S., Vaughan, D. G. and Okumoto, M. y. Pharrn. Sci. 45 93 (1956). (12) Crompton, D. O., Anderson, K. F. and Kennare, A. Cited by Crompton, D. O. Austral. y. Pharm. (30 October 1962). (13) Fisher, K. and Allen, H. F. Am. y. Ophthalrnol. 46 249 (1958). (14) United States National Formulary XI. Chapter on Ophthalmic Solutions. (15) Hugill, P. R., Osheroff, B. O. and Skolaut, M. W. Am. y. Hosp. Pharrn. 17 (September 1960). (16) Ridley, F. Brit. J. Ophthalmol. 42 641 (1958). (17) Lehrfeld, L. and Donnelly, E. J. Am. J. Ophthalmol. 31 470 (1948). (18) Editorial Lancet 647 (23 March 1963). (19) Ogg, A. J. Lancet 96 (13 July 1963). (20) Norton, D. A. Pharrn. y. 189 86 (1962). (21) Richards, R. M. E., Fletcher, G. and Norton, D. A. Pharm. y. 191 605 (1963). (22) Dale, J. K., Nook, M. A. and Barbiers, A. R. y. Am. Pharm. Ass. Pract. Pharm. Ed. 20 32 (1959). (23) Bean, H. S. and Heman-Ackah, S. M. Presented at the British Pharmaceutical Con- ference, Edinburgh, September 1964. To be published in J. Pharm. Pharmacol. Kohn, S. R., Gershenfeld, L. and Bart, M. J. Pharm. Sci. 52 967 (1963). Kohn, S. R., Gershenfeld, L. and Bart, M. J. Pharm. Sci. 52 1126 (1963). Editorial Pharm. J. 191 575 (1963). Klein, M., Millwood, E.G. and Walther, W. W. J. Pharm. Pharmacol. 6 725 (1954). Evans, W. P. J. Pharm. Pharmacol. 16 323 (1964). Lawrence, C. A. J. •/rn. Pharm. Assoc. Sci. Ed. 44 457 (1955). Anderson, K., Lillie, S. and Crompton, D. Pharm. J. 193 593 (1964). Foster, J. H. S. 21//. Pharm. Thesis (May 1964) (University of Nottingham). Hugo, W. B. and Foster, J. H. S. J. Pharm. Pharmacol. Suppl. 16 124T (1964). Davis, H. Quart. •. Pharm. Pharmacol. 7 361 (1935). Crompton, D. O. and Anderson, K. F. Lancet 1279 (14 December 1963). Richards, R. M. E. Lancet 42 (4 January 1964). Murphy, J. T., Allen, H. F. and Mangiaracine, A. B. Arch. Ophthalmol. 53 63 (1955). Anderson, R. A. and Stock, B. H. Austral. •. Pharm. (30 October 1958). Lilley, B. B. and Brewer, J. H. J. Am. Pharm. Assoc. Sci. Ed. 42 6 (1953).
THE PRESERVATION OF OPHTHALMIC PREPARATIONS 387 (39) Lawrence, C. A. Am. y. Ophthalmol. 39 385 (1955). (40) Ginsburg, M. and Robson, J. M. Brit. y. Ophthalmol. 33 574 (1949). (41) Runti, C. Boll. Chim. Farm. 99 286 (1960). (42) Buschke, W. y. Cellular and Comp. Physiol. 33 145 (1949). (43) Anderson, K. F., Lillie, S. and Crompton, D. O. Pharm. y. 193 165 (1964). (44) Swan, K. C. Am. J. Ophthalmol. 27 1118 (1944). (45) Hughson, D. T. and Styron, N. C. Am. y. Ophthalmol. 32 102 (1949). (46) Bell, R. P. Am. y. Ophthalmol. 34 1321 (1951). (47) Wiggins, R. L. Am. y. Ophthalmol. 35 83 (1952). (48) Jeffs, P. L. Austral. y. tharm. (30 March 1959). (49) Jeffs. P. L. Pharm. Digest 28 242 (May 1964). (50) Anderson, R. A. Pharm. y. 193 148 (1964). (51) Wiseman, D. Personal Communication. (52) Croshaw, B., Groves, M. J. and Lessel, B. y. Pharm. Pharmacol. Suppl. 16 127T (1964). (53) Davey, B. B. and Turner, M. y. Appl. Bacteriol. 24 78 (1961). (54) Schradie, J. and Miller, O. H. y. Am. Pharm. Assoc. Pract. Pharm. Ed. 20 197 (1959). (55) Lowbury, E. J. L. Brit. y. Ind. Med. 8 22 (1951). (56) Jawetz, E. and Gunnison, J. B. tharmacol. Rev. $ 175 (1953). (57) Garrett, E. R. Antiblot. Chemotherapy 8 8 (1958). (58) Hugo, W. B. and Foster, J. H. S. y. Pharm. Pharmacol. 15 79 (1963). (59) MacGregor, D. R. and Elliker, P. R. Can. y. Microbiol. 4 499 (1958). (60) Brown, M. R. W. and Richards, R. M. E. y.'Pharm. Pharmacol. Suppl. 16 41T (1964). (61) Brown, M. R. W. and Richards, R. M. E. J. Pharm. tharmacol. Suppl. 16 51T (1964). Introduction by Dr. M. R. W. Brown I would like to draw attention very briefly to some of the more important elements. The ideal preservative should be effective against a wide range of organisms, must not be irritant, or in any way harmful to eye tissues, must be compatible with other medicaments and should withstand sterilization, preferably by a heat method, with- out production of harmful degradation products. Furthermore, careful distinction must be made between materials used for continuous application to intact eyes, and the solutions used on damaged eyes or during surgery. The latter solution should be sterile and should not contain preservatives. Since this paper was submitted, we have been made aware of the recent work of Abrams (62) related to mercurialentis. He found that mercurialentis was slow to develop and no instance was found in glaucoma patients using myotics containing P.M.N. for less than three years. He furthermore stated, "as far as is known the appearance (mercurialentis) is not associated with any visual impairment and seems to be quite innocuous." There is scientific evidence to support the use of the following preservatives in appropriate instances: Benzalkonium chloride, phenylmercuric nitrate, thiomersal, chlorbutol, chlorocresol. At present there appears to be no scientifically based evidence to completely preclude their use under the controlled conditions of an ophthalmic formulation. Reports from Australian workers indicate decomposition of chlorhexidine on autoclaving, and the production of degradation products the freedom of which from toxicity has not been fully established and this would suggest caution regarding heat sterilization of preparations containing this compound. The employment of these substances must be subject to normal considerations of formulation and compatibility and, of course, to correct clinical usage. There (62) Abrams, J. D. Trans. Ophthalm. Soc. 83 263 (1963).
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