There is a suggestion on the literature that the formation of ion pairs creates a permeation enhancement. Usually only non-ionised compounds penetrate the skin. Is it possible that the conjugate species does so? Some sources claim the epolamine salt has enhanced solubility, others say it is about the same. Appreciate any help

  • $\begingroup$ Where does the literature suggest this? Would you be able to add a link? $\endgroup$
    – Curt F.
    Dec 13, 2018 at 19:06
  • $\begingroup$ They likely penetrate the skin as a rather unpolar pair of two large ions, where the organic rest shields the charges. $\endgroup$
    – Karl
    Apr 12, 2019 at 20:59

2 Answers 2


Voltaren is a 1 -2% paste of the ammonium salt of diclofenac (epolamine is hydroxyethyl pyrrolidine) and is used a topical pain reliever. You can smell the ammonia.

It could be that the increased pH of the paste softens skin and makes it more permeable. High pH will peel your skin right off!


Transdermal drug delivery is a complicated process governed not only by chemistry/physics, but also biology. Limiting ourselves to the physical/chemical aspects:

  1. Different solubility, both kinetic and thermodynamic
  2. Different tonicity - alters the osmotic pressure
  3. Different pH and buffering capacity of the formulation - altering charge state populations of the solutes in the local environment
  4. Surfactant effects of different solutes - changes the surface tension at phase interfaces
  5. Membrane perturbation by different solutes - ability to alter skin/cellular membrane behavior and dynamics

These factors are interrelated with one another to varying degrees

As for primary literature, see: Ex vivo study of transdermal permeation of four diclofenac salts from different vehicles


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