The aim of this work was to investigate the transdermal gel loaded with tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5) in order to improve the solubility and bioavailability. The solubility of tadalafil in mixed solution of hydroxypropyl-β-cyclodextrin (HPCD), polyethylene glycol (PEG) 400 and tween 80 (T2 solution) was 260.8 ± 4.3 µg/mL and that of tadalafil in modified T2 (M-T2) solution, which tadalafil was dissolved in 20% (w/v) HPCD at first and then mixture solutions of PEG 400 and tween 80 were added, was increased to 344.9 ± 30.6 µg/mL. Four gel formulae were prepared, subsequently in vitro and in vivo skin permeation studies were carried out. Interestingly, tadalafil gel in M-T2 and oleic acid (OA) (F3) could promote the percutaneous absorption of tadalafil by 179.4% in vitro and increase AUC by 223% in vivo compared with tadalafil gel in the absence of M-T2 and OA (F1). Also, there was a finding that tadalafil gel in M-T2 and OA did not cause dermal irritations in an experimental animal.
Keywords: Hydroxypropyl-β-cyclodextrin; pharmacokinetic; solubility; tadalafil; transdermal drug delivery.