392 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS DR. BROWN: I agree completely with the first part of your remarks. I would just like to comment on your remark that we do not like combinations, as I do not think this is correct. We have stated that they should not be used indis- criminately. A great deal of work has been done on synergism, antagonism, and additive action. It was originally thought that if you had one antibiotic that killed cells in the body and another one that did the same, then obviously the two together would be twice as good. This, of course, was not true and we were merely referring to the fact that they should not be combined indiscriminately. I agree that any organism which is happily surviving in the presence of the preservative, should be regarded as potentially dangerous. I only made the remark because I thought that Mr. Jeffries was perhaps referring to Aerobacta, and not A chrornobacter. We were rather timid about our reference to breakdown of chlorhexidine because the literature contains too many personal communications and statements of opinion. Nevertheless we have it on good authority that heating chlorhexidine in solution and autoclaving it, did in fact produce compounds which could well be toxic and that this would have to be examined before using this method. This would not preclude the use of chlorhexidine in a filtered solution, or sterilizing in some other way. I do not know whether these degradation products are harmful to the bacteria. MR. A. G. HOPKINS : At the present time quaternary ammonium compounds are becoming suspect as causing indurated ulcers, especially in damaged tissue. Does this not rule out substances like benzalkonium chloride, cetrimide, etc. ? DR. BROWN: We have heard about many defects of the quaternary ammonium compounds, particularly benzalkonium chloride. It has been stated, for example, that it dissolves the intercellular cement of the cornea. I have never heard of this particular problem but I think perhaps the problem is eliminated if, when using the damaged eye, no preservative at all is used unless it is absolutely necessary. Certainly during an operation when you are irrigating, say, the anterior chamber, you should use sterile saline or sterile water, or whatever it is that is required, without any preservative. What real evidence there is about this type of ulcer I do not know. Is it more than a report ? MR. A. G. HOPKINS: It is quite factual and there have been some reports in the last two or three weeks on this. In fact the use of Dequadin, Dequalinium chloride and even cetrimide is being curtailed because of these reports. I do not know whether anyone else has heard anything about this. DR. BROWN .' In America benzalkonium chloride has been used for a good number of years as a preservative of choice, and has been the official preservative. There are a good number of hospitals in America and I should have thought that benzal- konium chloride had been exposed to sufficient possibilities causing problems, to have really stood the test. We have only been able to find about two cases where there was proof that a resistant strain to benzalkonium chloride had arisen. I think it is easy, if you abuse the techniques, to produce resistant strains to benzolkonium chloride. MR. J. A. MYERs: Are you now in a position to suggest a suitable preservative for any of the eye drops in the British Pharmaceutical Codex ? DR. BROWN: We would like to suggest, and I am not sure, that the B.P.C.

THE PRESERVATION OF OPHTHALMIC PREPARATIONS 393 Committee agrees, that each preparation be regarded in its own right and to eliminate the attitude of "which is the best preservative ?" lXlot to say, "we will use chlorhexidine, or we will use phydroxybenzoates," but to look at each particular compound, and at each formulation, because each formulation could be different and could involve the necessity of using a different kind of preservative. It is therefore advisable to have in one's armoury as many preservatives as possible and not to eliminate any unless one has to. I think that this is the approach that will be taken in England from now on, i.e. that we will look at each pre- paration and consider it on its own merits. This, as Professor lXTeuwald has mentioned, occurs in Austria. MR. W. TRI•-•-wooo: It seems to me that we are very little further forward than we were •.0 years ago. We do not have a suitable container, we have one or two eye drops that are available as single dose containers, if we can call it that. I think we have surely reached the stage when, for surgical theatre work on damaged eyes, it must be a single dose container and yet we are limited to perhaps five drugs if we do this. We then turn to the things which are available commercially none of these, as far as I know, are available in a single drop container. The point has been made about the improper use in hospital of injections by nurses. I wonder if it is generally realized what kind of a moving population we have to deal with in hospitals. The nurses are moving all the time they are in training. We have moving populations of medical staff, too. And whatever drill one lays down today is obsolete tomorrow unless people are continuously watched. With eye drops it is even worse. They are left in the hands of patients. They are liable to touch the margin which may be contaminated, and after the first drop is used, the dropper is put back again and the contents are contaminated. These are the practical problems we are up against in hospitals. For damaged eyes one must suggest single drop containers as far as possible, and the smallest possible container. DR. BRowN: I believe there are single dose units on the market, and I believe that a B.S.S. for multidose containers is on its way. Mr. Norton has details of it. MR. F. BROPHY: I confirm that there are already a small number of g ml single dose phials available on the British market, which are completely sterile. A balanced salt solution, which is completely sterile, is also shortly to be available here. MR. D. A. NORTON : A committee of the British Standards Institution has been investigating pharmaceutical containers for the last two years or so, and one of the subcommittees has been dealing with the multidose eye drop container. We recognize, I think, that the need for extemporaneously prepared preparations will go on for some time and this standard recognizes it. The main aim of the speci- fication is to produce a bottle which will withstand autoclaving when properly sealed and with the medicaments contained therein. This was the requirement for auto- claving laid down some time ago in earlier papers. I hope that this specification will be published quite shortly, and I understand that almost final agreement has been reached on this standard. DR. HARRIS : The question concerning corneal ulceration following quaternary ammonium compounds is, I think, one of concentration. Some work has been published on this. Some work was done in Australia where I believe it was shown fairly clearly that the concentration normally used to preserve eye drops does not really give any trouble, not even over long periods.