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

• Published in: European journal of pharmaceutical sciences Vol. 151; p. 105410
• Main Authors: Chen, Xiao, Zhu, Lin, Li, Ruiteng, Pang, Lulu, Zhu, Siqing, Ma, Jinqiu, Du, Lina, Jin, Yiguang
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2020
• Subjects: Cumulative penetration; Electroporation; Mathematical simulation; Transdermal drug delivery; Cumulative penetration; Transdermal drug delivery; Electroporation; Mathematical simulation
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2020.105410

•A mathematical model between the cumulative permeation under electroporation and physiochemical properties of drugs was established, including pKa, logP and molecular weight.•The electroporation could cause the formation of reversible channels or pores in stratum corneum of skin, and the permeation effect can last for more than 12 h. 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. [Display omitted]