Electroporation-enhanced transdermal drug delivery: Effects of logP, pKa, solubility and penetration time

Electroporation is an important physical technique to improve drug transdermal delivery, although its mechanism remains unclear. Here, some types of polar drugs, including aspirin, diclofenac sodium, metformin hydrochloride, ibuprofen and zidovudine, were used as the model drugs for the exploration of electroporation mechanisms. Electroporation had great influences on the structure of stratum corneum to improve the cumulative permeability due to the formation of pores maintaining for at least 2 h, depending on the power and time, and then the permeation gradually recovered to the normal value after 12 h. A mathematical model was firstly established to exhibit the relationship between the electroporation-improving cumulative permeation and the physiochemical properties of the model drugs, involving oil-water partition coefficient (logP), dissociation constant (pKa) and solubility (S). Increased cumulative permeation depended on increased S, decreased logP and pKa. Electroporation is an effective physical technique to improve transdermal drug delivery depending on itself and the properties of drugs.