Description of transdermal transport of hydrophilic solutes during low-frequency sonophoresis based on a modified porous pathway model

J Pharm Sci. 2003 Feb;92(2):381-93. doi: 10.1002/jps.10299.


Application of low-frequency ultrasound has been shown to increase skin permeability, thereby facilitating delivery of macromolecules (low-frequency sonophoresis). In this study, we sought to determine a theoretical description of transdermal transport of hydrophilic permeants induced by low-frequency sonophoresis. Parameters such as pore size distribution, absolute porosity, and dependence of effective tortuosity on solute characteristics were investigated. Pig skin was exposed to low-frequency ultrasound at 58 kHz to achieve different skin resistivities. Transdermal delivery of four permeants [mannitol, luteinizing hormone releasing hormone (LHRH), inulin, dextran] in the presence and absence of ultrasound was measured. The porous pathway model was modified to incorporate the permeant characteristics into the model and to achieve a detailed understanding of the pathways responsible for hydrophilic permeant delivery. The slopes of the log kp(p) versus log R graphs for individual solutes changed with solute molecular area, suggesting that the permeability-resistivity correlation for each permeant is related to its size. The tortuosity that a permeant experiences within the skin also depends on its size, where larger molecules experience a less tortuous path. With the modified porous pathway model, the effective tortuosities and skin porosity were calculated independently. The results of this study show that low-frequency sonophoresis creates pathways for permeant delivery with a wide range of pore sizes. The optimum pore size utilized by solutes is related to their molecular radii.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Cutaneous*
  • Algorithms
  • Animals
  • Chemistry, Pharmaceutical
  • Dextrans / administration & dosage
  • Dextrans / pharmacokinetics
  • Diffusion
  • Excipients
  • Gonadotropin-Releasing Hormone / administration & dosage
  • Gonadotropin-Releasing Hormone / pharmacokinetics
  • In Vitro Techniques
  • Inulin / administration & dosage
  • Inulin / pharmacokinetics
  • Lipid Bilayers
  • Mannitol / administration & dosage
  • Mannitol / pharmacokinetics
  • Models, Biological
  • Molecular Weight
  • Porosity
  • Skin Absorption / physiology*
  • Swine
  • Ultrasonics*


  • Dextrans
  • Excipients
  • Lipid Bilayers
  • Gonadotropin-Releasing Hormone
  • Mannitol
  • Inulin