304 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 150 100 50 20 PEG-4000 /'•PEG-1500 PEG-6000///PEG-400 Lac. DiPG Acid 1 o3-BG Urea PG Glycerin Glycine . • '•,u•,•f•,• - Lac-Na - 5 10 Concentration of Additives (w/v %) Figure 7. Effect of various additives on concentration of free BP (Cw) in 3w/v% OE-515 aqueous solution containing 0.4w/v% total BP. In Figure 8, the effect of additives on the cloud point of surfactant and Cw of BP are shown together with the antimicrobial activity of BP against Candida albicans. The additives can be classified into four groups according to their effect on the cloud point, Cw, and the antimicrobial activity against Candida albicans as follows: I) Additives such as 1.3-BG, PG, urea, etc. which raise the cloud point and strengthen the antimicrobial activity of BP by increasing Cw. II) Additives such as PEG which reduce the antimicrobial activity of BP in spite of increasing Cw. III) Additives such as KC1, PCA-Na, glycine, etc. which lower the cloud point and reduce the antimicrobial activity of BP by decreasing Cw. IV) Polar oil additives such as RA.TM-318, RA.PE-408, etc. which raise the cloud point and reduce the antimicrobial activity of BP by decreasing Cw. These relationships are illustrated in Figure 9. When the additives are absent, the BP molecule is considered to be solubilized within the polyoxyethylene mantle of surfactant micelies.

ANTIMICROBIAL ACTIVITY OF BUTYLPARABEN 305 f Q / O 3.0 w/v% 200 / / BP 0.4 OE-515 w/v% / Additive 0--10w/v% o/ PEG4000 • ot 150 - '" ,,,• PEG-6000 J • •/ •$ _ 50[ Lac Na (•f l/ •RA.T• 318 :"••/• No•l/Additie •RA-PE-408 61yc•e KC• ii I I I i i i i 0q•0 40 50 60 70 80 90 100 Cloud Point (øC) Figure 8. Effect of various additives on cloud points of 3w/v% OE-515, Cw of BP, and antimicrobial activity of BP against Candida albicans. O: no growth A: •veak growth X: growth. o Ie Figure 9. Schematic illustration for effect of various additives on solubilization behavior of BP. 44a-: surfactant molecule •5-: BP molecule O G: water-soluble molecule •: PEG molecule -: water- insoluble molecule: (polar oil).