734 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS paper wrappings can be protected from spoilage by the incorporation of a preservative into them, but this is not entirely without difficulties. CONCLUSIONS Microbial spoilage of pharmaceuticals and cosmetics is significant both from health and economic viewpoints and obviously should be prevented. It is dear that disease-causing organisms must be excluded, although sometimes it may be difficult to decide if an opportunist pathogen will be troublesome in a specific product. The situation with regard to spoilage micro-organisms, in the strict sense, is less dear as much is still to be learnt about the biochemical and microbiological mechanisms involved certainly there is room for further fundamental studies in this fascinating field. Deleterious changes will be avoided, of course, if all microbes are excluded from a product but it is not practicable to treat most pharma- ceuticals and cosmetics as sterile products. Indeed, neither may this be desirable as we do not live in a sterile world and products, like human beings, must also survive in the presence of some micro-organisms. This raises the difficult question of how many organisms of what sort are accept- able in a given product. Several millions of organisms per gram are usually present in foods before decomposition reaches the point where it is detect- able to the senses (26) and this is generally also true of liquid pharma- ceuticals and cosmetics. It also applies to more solid products where, although organisms may be concentrated at a focus, nevertheless they have to be present in some millions before the resulting colonies become trouble- some. Contamination of pharmaceuticals and cosmetics with fewer cells may herald populations of spoilage potential if the contaminants can multiply this is a matter of experience and experiment. Preservatives cannot always be relied upon to prevent the multiplication of micro- organisms because the ideal universal preservative does not exist and there- fore the choice for each product is an individual, and often not entirely successful, matter. In any case preservatives are no substitute for good hygiene during production. Lower viable counts in a product may represent the survivors of a larger population which has already caused decomposition but this is often obvious. A few hundred viable organisms per gram are generally of little consequence. The presence of many thousands of organisms, however, is usually a matter of concern as a count of this magnitude frequently in- dicates that spoilage will occur. To attempt to define more precise numerical

MICROBIOLOGICAL SPO1LAGE IN 'PHARMACEUTICALS AND COSMETICS 735 limits which are meaningful and yet can be applied generally to pharma- ceutical and cosmetic products is extremely difficult, if not impossible, in view of the multiplicity of organisms and products involved. In practice, regular monitoring during development and manufacture establishes the type and minimum number of organisms which are achiev- able for each specific product. Providing, of course, that this level is compatible with microbiological stability it forms the best approximate guide-line for a product. (Received: 13th June 1971) REFERENCES (1) (2) (3) (4) (5) (6) (7) (8) (9) (1o) (11) (12) (13) (14) (15) (16) (17) (•8) (19) (20) (21) Butler, N.J. The microbiological deterioration of cosmetics and pharmaceutical products. In Biodeterioration of Materials 269 (1968) (Elsevier Publishing Co., Amsterdam, London and New York). Sykes, G. Microbial contamination in pharmaceutical preparations for oral and topical use. Indian J. Pharmacy 31 No. 2 33 (1969). Barnes, J. M. Aflatoxin as a health hazard. J. Appl. Bacteriol. 33 285 (1970). Perlman, D. and Peruzzotti, G. P. Microbiological metabolites as potentially useful pharmacologically active agents. In Advances in Applied Microbiology 12 277 (1970) (Academic Press, New York and London). Smith, G. N. and Worrel, Celia S. Studies on the action of chloramphenicol on enzymatic systems. Archives Blochem. 23 No. 1 341 (1949). Hugo, W. B. The degradation of preservatives by micro-organisms. Sci. Tech. Symp. 122 112th Ann. Mtg Am. Pharm. Assoc. C411, 1 (1965). Kedzia, W., Lewon, J. and Wisnienski, T. The breakdown of attopine by bacteria. J. Pharm. Pharmacol. 13 614 (1961). Grant, D. J. W., de Szors, J. and Wilson, J. V. Utilization of acetylsalicylic acid as sole carbon source and the induction of its enzymatic hydrolysis by an isolated strain of Acinetobacter lwoffi. J. Pharm. Pharmacol. 22 No. 6 461 (1970). Omelianski, V. C. Aroma-producing micro-organisms. J. Bacteriol. 8 No. 4 393 (1923). Gerber, N. N. and Lechevalier, H. A. Geosmin, an earth-smelling substance isolated from actinomycetes. Appl. Microbiol. 13 935 (1965). Margalith, P. and Schwartz, Y. Flavor and micro-organisms. In Advances in Applied Microbiology 12 35 (1970) (Academic Press, New York and London). Shooter, R. A., Cooke, Mary E., Gaya, H., Kumar, P. and Patel, N. Food and medica- ments as possible sources of hospital strains of Pseudomonas aeruginosa. Lancet i 1227 (1969). Guyne, C. J. and Bennet, E. O. Bacterial deterioration of emulsion oils. Appl. Microbiol. 7 117 No. 2 (1959). Bean, H. S. The microbiology of topical preparations in pharmaceutical practice. 2. Pharmaceutical aspects. Pharm. J. 199 No. 5 421,289 (1967). Bart, M. and Tice, L. F. The preservation of aqueous preparations containing non-ionic surfactants I. J. Am. Pharm. Assoc. Sci. Ed. 46 No. 7 442 (1957). Tice, L. F. and Barr, M. Factors to be considered in the preservation of cosmetic emulsions. J. Soc. Cosmet. Chem. 9 171 (1958). Wedderburn, D. L. Preservation of emulsions against microbial attack. In Advances in Pharmaceutical Sciences 195 (1966) (Academic Press, London). Rivers, S. M. and Waiters, V. The effect of benzoic acid, phenol and hydroxybenzoates on the oxygen uptake and growth of some lipolytic fungi. J. Pharm. Pharmacol. 18 supp. 45S (1966). Eggins, H. O. W. and Walters, V. The decomposition of pharmaceutical emulsions by fungi. W. African J. Biol. Appl. Chem. 7 No. 1 2 (1963). Bryce, D. M. and Smart, R. The preservation of shampoos. J. Soc. Cosmet. Chem. 16 187 (1965). Walker, H. W. and Ayres, J. C. Yeasts as spoilage organisms. In The Yeasts 3 463 (1969) (Academic Press, London and New York).