Lineweaver-Burk analysis of skin penetration enhancement

The transdermal penetration of propranolol hydrochloride across hairless mouse skin in vitro has been enhanced using n-nonane (C9), 1-nonanol (C9OH), 1-dodecylazacycloheptan-2-one (AZ), and oleic acid (OA). For each enhancer, the maximum rate of drug permeation (J_m) was determined as a function of enhancer concentration in the vehicle (ethanol). It was found, that, in all cases, skin penetration enhancement was saturable; that is, the augmentation of propranolol flux reached a maximum at higher enhancer concentrations that could not be increased by further increase in the amount of enhancer applied. The data were analyzed using a technique borrowed from enzyme kinetics, the Lineweaver-Burk plot, in which 1/J_m was plotted against the reciprocal of the enhancer concentration used. It was found that the y-axis intercepts, which correspond to the reciprocal of the maximum rate (1/V_max), were remarkably consistent between the 4 enhancers considered. The slopes (equivalent to K_m/V_max), however, were enhancer-dependent, and indicated that the K_m values for AZ and OA were about an order of magnitude less than those for C9 and C9OH. The results imply, therefore, that AZ and OA are significantly more effective enhancers than C9 and C9OH. These results suggest that the data analytical approach employed may have practical utility for classifying the relative potency of putative skin penetration enhancers.