On the possibility of therapeutic action after transdermal patch application

Background. As scientific knowledge about the peculiarities of the structure and functional properties of the skin increased, it became clearer that during transdermal administration, drug may accumulate in the deep layers of the dermis and subsequently get diffused into the bloodstream even after the transdermal therapeutic system (TTS), also called transdermal patch, had been removed. Objective: to quantify active drug substances remaining in an animal skin after TTS application. Materials and methods. Two previously developed transdermal patches containing Russian-made drug substances were chosen for the study: aminodihydrophthalazinedione sodium (immunomodulator) and bis(1-vinylimidazole-N) zinc diacetate (antidote for carbon monoxide). The study was performed on male Chinchilla rabbits weighing 2.5–3 kg. Five series of experiments were performed for each substance: immediately after removal of the patch, 4 hours later, at week 1, 2 and 3 after removal. High-performance liquid chromatography and atomic absorption spectroscopy methods were used to quantify residual drug substances left in the skin. Results. In the skin flap that was in contact with the aminodihydrophthalazinedione sodium TTS for 24 hours, 0.516 mg of the drug was detected immediately after removal of the patch. Over the next two weeks, the drug substance in the skin decreased with the immunomodulator significantly reducing to 0.41 mg in the first 4 hours. In the skin flap that had been in contact with zinc bis(1-vinylimidazole-N) diacetate for 24 hours, about 1 mg of the drug was present immediately after patch removal. Four hours after removal of the transdermal patch, the quantity of active substance in the skin remained practically unchanged. At week 1 and 2, the quantity of the antidote decreased slightly to ~0.7 mg and ~0.25 mg, respectively. Conclusion. For transdermal application of aminodihydrophthalazinedione sodium, the skin can act as a drug depot and prolong the effect of this drug even after the transdermal patch had been removed. No such effect was found in the case of bis(1-vinylimidazole-N) zinc diacetate, which is apparently due to the different solubility of the drugs in the biotissue.