Chemical permeation enhancers (CPEs) can enable antibiotic flux across the tympanic
membrane. Here we study whether combinations of CPEs (sodium dodecyl sulfate,
limonene, and bupivacaine hydrochloride) are synergistic and whether they could increase
the peak drug flux. Synergy is studied by isobolographic analysis and combination indices.
CPE concentration-response (ie trans-tympanic flux of ciprofloxacin) curves are
demonstrated for each CPE, isobolograms constructed for pairs of CPEs, and synergy …

Synergistic combinations of chemical penetration enhancers are important considerations in
drug formulation because they can greatly influence transdermal drug delivery, positively or
negatively. This chapter describes how synergistic actions between chemical penetration
enhancers can be defined, discovered and measured. The chapter considers literature
reports where both positive and negative synergism between chemical penetration
enhancers have been described. The underlying mechanisms of action that result in …