Percutaneous absorption and skin erythema: Quantification of capsaicin and its synthetic derivatives from gels incorporated with benzalkonium chloride by using non-invasive bioengineering methods

Nonivamide (NVA) and sodium nonivamide acetate (SNA) are synthetic derivatives of capsaicin. In this study, the cationic surfactant benzalkonium chloride was incorporated into the Carbopol 940® gel bases of capsaicin and its synthetic derivatives to evaluate the in vitro percutaneous absorption capacity. Afterwards, the optimal gel formulation selected from the in vitro study was used in a series of in vivo non-invasive bioengineering methods. To quantify the skin erythema and irritation caused by capsaicin, NVA, and SNA, laser Doppler flowmetry (LDF), transepidermal water loss (TEWL), and colorimetry were utilized for determining the cutaneous blood flow and skin barrier impairment to assess the level of irritant reaction. In the in vitro transdermal study, the gel base with 0.05% benzalkonium chloride possessed the highest penetration capacity: this was chosen for the in vivo study. After quantification of skin erythema by LDF, capsaicin developed more severe irritation than NVA, and SNA showed no skin irritation or pungent sensation in volunteers. The result of the TEWL experiment suggested that 0.05% benzalkonium chloride did not cause any skin impairment. Moreover, the Carbopol 940® gel base itself offered a moderate penetration capacity for drugs and avoided any skin irritation. The result of colorimetry confirmed that both Δa* and ΔE* parameters correlated well with the data of LDF and that they are good indicators of skin erythema response. After a series of in vivo applications, SNA was shown to be a potent analogue of capsaicin with a marked pharmacological effect and moderate percutaneous capacity and reduced skin erythema and painful sensation. Drug Dev. Res. 40:56–67, 1997. © 1997 Wiley-Liss, Inc.