FORMULATION AND PROPERTIES OF CHLORHEXIDINE 2?3 the site at which pathogens reside and a contributory factor may be in- activation by pus or tissue debris. TOILET PREPARATIONS At the present time only a minor fraction of the total chlorhexidine out- put is diverted to retail products but this is expected to increase now that it has become fully established in the medical and veterinary fields. Examples of the various applications of the three available salts are: hydro- chloride in Savlon baby powder and Mimospray deodorant (the acetate and gluconate may also be used in sprays) and the gluconate in Savlon baby lotion and in antiseptic solutions such as Savlon liquid antiseptic. In the latter connection there was a problem to convert a colourless, odour- less, chemical into a typical antiseptic solution by incorporating a strong antiseptic perfume, with appropriate colour, a matter which entailed much close attention to the solubilization of essential oils and the conducting of user acceptance trials. In relation to the deodorant field and the rapidly extending market for feminine hygiene products (39), the researches of Morris and Maclaren (40) are noteworthy. These clinicians compared chlorhexidine (0.1•o hydro- chloride) and hexachlorophane (0.2•o) deodorant sprays on 64 women in a cross-over: test on two groups, to the total exclusion of all other antibac- terial preparations. They reported that 'the chlorhexidine spray caused a marked reduction in perineal flora whereas the hexachlorophane spray caused virtually no alteration', concluding that the comparative ineffective- ness of the latter against Gram-negative organisms was a serious dis- advantage. A valuable safety factor with chlorhexidine as a toilet aid is the assurance that significant systemic absorption does not take place. ORAL HYGIENE The main aim of this communication is to survey the circumstances in which chlorhexidine is applied to the skin, its effectiveness and the type of formulations which have been developed. However, an up-to-date appraisal would be incomplete without a reference to the recent researches in the field of oral hygiene. Current oral antiseptic preparations are largely intended for cleansing and deodorizing the mouth and their popularity has risen greatly during the past few years, especially in the U.S.A., though only moderately in the

274 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS U.K. A further possibility resulting from the suppression of oral micro flora is to prevent the onset of dental caries, with the fine ideal of lifelong reten- tion of the natural teeth. The mechanism of dental decay is not fully elucidated but much is known about it and the widely accepted theory is that the plaque which develops on the less accessible 'stagnation sites' harbours bacteria which degrade the residual sugar to organic acids. These in turn attack the enamel (essentially hydroxyapatite Caxo(PO4)6(OH)2), leaching out the calcium, diminishing the degree of hardness and permitting the ingress of cariogenic bacteria. Plaque therefore plays a decisive role in the initiation and development of caries and marginal periodontal disease. As long ago as 1953, Fosdick (41) postulated that anticaries agents (whether fluorides or antibacterials) were deposited on the plaque, where they were retained. It now seems that recent data are in support of these two essential requirements. Gjermo, Baastad and Rolla (42) compared the plaque inhibiting effect in vivo of eleven antibacterial agents (alcohols, iodophores, dyes, quater- naries, amidines and guanidines) with their bacterial activity against salivary bacteria in four in vitro systems to find that there was no connection between the results. Chlorhexidine gluconate and acetate were the most effective in vivo whereas others, more effective against bacteria in vitro, exhibited no effect in vivo. This led to the conclusion that other factors apart from anti- bacterial action were involved, and was in accord with the previous findings of Loe and Rindom Schiott and their colleagues at the Royal Dental College, Denmark, who regarded chlorhexidine as the most promising anticaries agent. Their choice was based upon its broad effects against bacteria and yeasts, low toxicity and widespread use in clinical medicine (43). A twice daily rinse with aqueous 0.2•o chlorhexidine gluconate in a 3-4 week study was shown to be effective in preventing plaque and calculus formation (45) yet they also found that, although the oral flora was markedly reduced (up to 90•o), large numbers of bacteria still persisted, from which it appeared unlikely that the inhibition of plaque formation was primarily the result of a reduction of salivary flora (45, 46). In some of these tests the mouth was rinsed with strong sucrose solution to provoke plaque forma- tion yet this did not diminish the efficacy of chlorhexidine. In a further study these workers (47) concluded that chlorhexidine gluconate was ad- sorbed on tooth surfaces and salivary mucins, from which it was slowly released when the environmental concentration was low. More recently it was shown that chlorhexidine adsorbed onto the plaque deposits within the space of a few seconds. When an extracted tooth,