372 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS not much is known about the quantitative correlation between the physieo- chemical properties of the substance and the degree of percutaneous absorp- tion (4). There are many factors that can alter the rate or extent of absorption into the skin. For example, the mode of application, temperature of the skin, in- fluence of the vehicle, frequency and duration of application, condition of the skin, and the concentration and physicochemical properties of the active in- gredient can all affect the absorption. If all but the last of the aforementioned factors can be kept constant, then it will be possible to determine which phsicochemical properties of the compound are most important in deter- mining the absorption through the skin or into the skin. The main purpose of this report is to show how in vitro and in situ percu- taneous absorption data of different types of drugs or organic compounds can be correlated with a number of physicochemical constants by using a computerized multiple regression analysis program. By comparing the equa- tions of different sets of data one can obtain some useful quantitative guide- lines in predicting percutaneous absorption. EXPERIMENTAL The absorption data and most of the chemical constants were taken from the literature. The log P (octanol/water) values were either experimentally determined or calculated by taking advantage of the additivity of rr constants (5-8). The absorption data were converted to log C, log 1/C or log K• Table I In Vitro Percutaneous Absorption of Phenylbornic Acids by Human Skin Acid Log P• Log pb Log C (Octanol/ (Benzene/ Water) Water) Obsd • Calcd c Diff Calcd a Diff m-Carbamidophenylboronic 0.57 . .. --3.73 --3.42 --0.31 ...... m-Carboxyphenylboronic 0.53 --2.53 --3.65 --3.45 --0.20 --3.52 --0.13 p-Carboxyphenylboronic 0.53 --1.83 --3.33 --3.45 0.12 --2.64 --0.10 m-Aminophenylboronic 0.43 --2.32 --3.24 --3.50 0.26 --2.a0 0.14 p-Methoxyphenylboronic 1.69 --0.43 --2.74 --2.78 0.04 --2.50 --0.09 Phenylboronic 1.58 --0.80 --2.66 --2 84 0.18 --3 43 0.19 p-Chloropheny]boronic 2 38 --0.09 --2.59 --2.38 --0.21 --3.23 --0.10 p-Methylpheny]boronic 2.06 --0.19 --2.45 --2.57 0.12 --2.54 0.09 P(octanol/water) calculated from the appropriate •- values (refs. 5, 6, 9). From ref. 10. Calculated from eq 1. Calculated from eq 3.

PERCUTANEOUS ABSORPTION OF DRUGS 373 (cm/hr), where C was the molar concentration measured or required to cause a standard biological response, and Kp was the permeability constant. For the detailed procedure of the absorption study the original references should be consulted. The absorption data and the physicochemical constants used in the regression analysis are assembled in Tables I-VI. The general Table II In Vitro Permeability of Nonelectrolytes through Rabbit Whole Skin and Rabbit Dermis Log P Whole Skin Dermis Compound Log MW Log MRa a (Octanol/ Log Kp (cm/hr) Log K• (cm/hr) Water) Obsd b Calcd c Diff Obsd b Calcd a Diff Ethyl iodide 2.19 1.39 2.00 Methanol 1.51 0.91 --0.66 Ethanol 1.6'6 1.11 --0.16 * Thiourea 1.88 1.14 -- 1.70 Glycerol 1.96 1.29 --2.56 Urea 1.78 1.32 --2.79 Glucose 2.26 1.58 --3.29 --2.26 --2.26 0.00 ......... --2.59 --2.70 0.11 --0.93 --0.97 0.04 --2.57 --2.63 0.06 --1.07 --1.05 --0.02 --3.76 --3.42 --0.34 --1.17 --1.18 0.01 --3.63 --3.82 0.19 --1.26 --1.23 --0.03 --3.84 --3.75 --0.09 -- 1.14 -- 1.12 --0.02 --4.27 --4.35 0.08 --1.37 --1.40 0.03 Calculated from the molecular refractivities given in ref. 11. From ref. 12. Calculated from eq 9. Calculated from eq 12. Experimentally determined values from ref. 13. Calculated value. Table III In Vitro Permeability of Aliphatic Alcohols through Human Epidermis Compound Log Ko • Log P Log K. Log Kp (cm/hr) (Octanol/Water) Obsd * Calcd a Dif[ Water ...... --0.52 --3.00 ...... Methanol --2.10 --0.66 c --0.22 --3.00 --3.24 0.24 Ethanol --1.52 --0.16 • --0.22 --3.00 --2.97 --0.03 n-Propanol --0.77 0.34 • 0.30 --2.85 --2.70 --0.15 n-Butanol --0.30 0.84 • 0.40 --2.60 --2.43 --0.17 n-Pentanol 0.70 1.34 t 0.70 --2.22 --2.16 --0.06 n-Hexanol 1.06 1.84 t 1.00 --1.89 --1.88 --0.01 n-Heptanol 1.79 2.34 t 1.48 --1.49 --1.61 0.12 n-Octanol 2.34 2.84 • 1.70 --1.28 --1.34 0.06 Ko = olive oil/water partition coefficient from ref. 14. K. ----- stratum eorneum/water partition eoefiieient from ref. 14. From ref. 14. Calculated from eq 14. Experimentally determined value from ref. 13. Calculated value.