PERCUTANEOUS-ABSORPTION AND SKIN ERYTHEMA - QUANTIFICATION OF CAPSAICIN AND ITS SYNTHETIC DERIVATIVES FROM GELS INCORPORATED WITH BENZALKONIUM CHLORIDE BY USING NONINVASIVE BIOENGINEERING METHODS

Nonivamide (NVA) and sodium nonivamide acetate (SNA) are synthetic der ivatives of capsaicin. In this study, the cationic surfactant benzalko nium chloride was incorporated into the Carbopol 940(R) gel bases of c apsaicin and its synthetic derivatives to evaluate the in vitro percut aneous absorption capacity. Afterwards, the optimal gel formulation se lected from the in vitro study was used in a series of in vivo non-inv asive bioengineering methods. To quantify the skin erythema and irrita tion caused by capsaicin, NVA, and SNA, laser Doppler flowmetry (LDF), transepidermal water loss (TEWL), and colorimetry were utilized for d etermining the cutaneous blood flow and skin barrier impairment to ass ess the level of irritant reaction. In the in vitro transdermal study, the gel base with 0.05% benzalkonium chloride possessed the highest p enetration capacity: this was chosen for the in vivo study. After quan tification of skin erythema by LDF, capsaicin developed more severe ir ritation than NVA, and SNA showed no skin irritation or pungent sensat ion in volunteers. The result of the TEWL experiment suggested that 0. 05% benzalkonium chloride did not cause any skin impairment. Moreover, the Carbopol 940(R) gel base itself offered a moderate penetration ca pacity for drugs and avoided any skin irritation. The result of colori metry confirmed that both Delta a and Delta E* parameters correlated well with the data of LDF and that they are good indicators of skin er ythema response. After a series of in vivo applications, SNA was shown to be a potent analogue of capsaicin with a marked pharmacological ef fect and moderate percutaneous capacity and reduced skin erythema and painful sensation. (C) 1997 Wiley-Liss, Inc.