A 
high throughput screening and 
isolation system identifies rare 
enhancer mixtures from a candidate 
pool of 
penetration enhancer combinations. The combinations are screened for high penetration but low 
irritation potential using a unique 
data mining method to find new potent and safe chemical 
penetration enhancer combinations. The members of a 
library of chemical 
penetration enhancer combinations are screened with a high 
throughput device to identify “hot spots”, particular combinations that show higher chemical penetration enhancement compared to neighboring compositions. The 
irritation potentials of the hot spot combinations are measured to identify combinations that also show low 
irritation potential. A 
active component, such as a 
drug, is then combined with the combination in a formulation which is tested for the ability of the 
drug to penetrate into or through 
skin. It is then assessed whether the formulation can deliver the quantity of 
drug required, and animal tests are conducted to confirm 
in vivo the ability of the chemical penetration 
enhancer combinations to facilitate transport of sufficient active molecules across the 
skin to achieve therapeutic levels of the active molecule in the animal's blood. The invention provides specific unique and rare mixtures of chemical penetration enhancers that enhance 
skin permeability to hydrophilic macromolecules by more than 50-fold without inducing 
skin irritation, such as combinations of 
sodium laurel 
ether sulfate and 1-phenyl 
piperazine, and combinations of N-lauryl 
sarcosine and Span 20 / 
sorbitan monolaurate.