356 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table IV Water Vapor Permeation through Ointment on Skin (Time in Min) Formula No.• Time Reading I 20 b -- 25 - 30 - 2 5b - 10 - 15 - 3 6• - 11 - 16 - 4 6• -- 11 -- 16 - 5 6• -- 11 - 16 - 8 6• -- 11 - 16 - 10 82o -- 85 90 +++ • Numbers of formulas refer to Table I. b Indicates the time for each preparation when the cooling effect, by means of in vivo curves, had fallen back to zero. formula, but showed no significant increase of cooling effect in vivo. The other modifications, those in which both the concentration o[ sodium borate and spermaceti were reduced, and those in which the sodium bor- ate concentration alone is varied, showed poor results in vitro, and for this reason were not tested in vivo. Figure 6 shows a graph of the in vitro data obtained for preparations 1.1-1.5 in relation to the USP XVIII in vitro result. CONCLUSION From the in vitro and in vivo testing it can be concluded that the in vitro test gives a good measure of in vivo effectiveness, and can be used as a screening technique [or determining which o[ several topical prepara- tions will have the best cooling action in vivo, although no direct quan- titative relationship was established [or all preparations. Although stable, elegant, and a good preparation from the viewpoint of pharmaceutical technology, the USP XVIII cold cream is a poor prep-

COOLING EFFECT OF COLD CREAMS Table V Modifications of Cold Cream USP XVIII- 357 Preparation No. Variation in Formula (in % of Quantity in USP XVIII Formula) Maximum Cooling Effect Atms• in vitro 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 lOO lOO lOO lOO lOO 75 75 5O 5O 5O 5O 25 12.5 6.25 B/75 S B/50 S B/25 S B/12.5 S B/6.25 S B/100 S B/75 S 75 B/50 S 75 B/25 S 75 B/12.5 S 75 B/6.25 S 50 B/100 S 50 B/75 S B/50 S B/25 S B/12.5 S B/6.25 S B/100 S B/100 S B/100 S 5.58 6.20 5.83 5 55 5 97 09 26 2 1 30 36 3 05 41 2.2 2.5 3.2 2.85 3.5 0.7 1.4 0.4 indicates sodium borate S indicates spermaceti. 0 I0 20 30 40 50 60 M•nutes Figure 6. Cooling curves in vitro of modified cold cream USP XVIII