A Systematic Quantitative Evaluation of Permeation Enhancement Window: Transdermal Permeation Enhancing Dynamics Establishment and Molecular Mechanisms Characterization of Permeation Enhancer

At present, transdermal permeation enhancing dynamics studies on permeation enhancers are still limited. In this study, these dynamics were established based on the content of enhancer Plurol Oleique CC in skin (CPOCC) and the increment of drug permeation amount (ΔQ). A new concept deemed "permeation enhancement window" (ΔCPOCC), comprised of a threshold dose (Cthr), maximal dose (Cmax) and permeation enhancement efficiency (Eff) was used to evaluate the enhancement effect of POCC for different drugs. According to results of FT-IR, ATR-FTIR and DSC analyses, the higher CPOCC of patches containing acidic drugs vs. basic drugs resulted from their stronger interaction with pressure-sensitive adhesives, leading to more free POCC and a greater disturbing effect on stratum corneum (SC) lipids. Below Cthr, a longer lag phase for acidic drugs resulted from more POCC required to compete with ceramide. When CPOCC exceeded Cmax by about 400 μg/g, plateau phases for all drugs were reached due to the upper limit of SC lipid fluidity, as confirmed by SAXS and Raman imaging. In summary, the differences in the permeation enhancement window for the test drugs resulted from the varied interaction strengths among POCC, drugs and adhesives, as well as changeable SC lipid fluidity.