Abstract
Purpose: The aim of this study
was to find a relationship between drug solubility and its transdermal
permeation and find the best vehicle composition to improve transdermal
permeation of Tadalafil.
Methods: Pure or binary
mixtures of commonly used solvents in pharmaceutical sciences including
ethanol, glycerin, N-methyl pyrrolidone (NMP), polyethylene glycol (PEG) 400
and propylene glycol (PG) were evaluated for drug solubility and transdermal
delivery through the exercised rat skin employing Franz diffusion cells.
Results: Tadalafil showed higher solubility in NMP compared
to the other solvents. The amount of Tadalafil permeation from the pure
vehicles was ranked as follow: Ethanol >glycerin >NMP>PEG 400
>PG. Furthermore, the solubility and transdermal delivery from binary
mixtures of NMP and PG were higher than that obtained from pure PG, and
accordingly, both increased with increasing NMP concentration in the binary
solvent mixtures. The Flux values were determined as following order for
Ethanol>NMP>glycerin>PG>PEG 400.
Conclusion: Generally, increase
in Tadalafil solubility resulted in a decrease in its skin penetration rate and
amount. However, NMP exhibited substantial drug skin penetration rate and
amount accompanying with appropriate drug solvency. In conclusion, the results
of this study introduced NMP as a solvent suitable for application in the
formulation of topically applied drug delivery systems.