Effect of novel penetration enhancers on the transdermal delivery of hydrocortisone: An in vitro species comparison

Six novel compounds were examined for enhancer activity using occluded hairless mouse skin (HM), hairless rat skin (HR), human cadaver skin (HC) in vitro with hydrocortisone as the model drug. The compounds investigated included: N-dodecyl-2-pyrrolidinone (DPY), N-dodecyl-2-piperidinone (DPI), N-dodecyl-N-(2-methoxyethyl)acetamide (DMEA), N-dodecyl-N-(2-methoxyethyl)isobutyramide (DMEI), N-dodecyldiethanolamine (DDE), 2-(1-nonyl)-1,3-dioxolane (ND), and Azone(R). Controls consisted of no enhancer or vehicle treatment. All enhancers were applied at 0.4 M in propylene glycol 1 h prior to skin application of a saturated suspension of hydrocortisone in the same vehicle. Enhancement ratios (ER) were determined for 24 h diffusion cell receptor concentrations (Q(24)), permeability coefficients (P), and 24 h full-thickness skin steroid contents. ER for controls was 1.0. N-dodecyl-2-pyrrolidinone (DPY), an Azone(R) analog, showed the greatest ER values for permeability coefficient (HM: 21.3, HR: 20.7, HC: 8.0) compared to control (ER: 1.0) and Azone(R) (HM: 18.0, HR: 13.1, HC: 5.5) in all three animal skin models. All six enhancers exhibited poor skin steroid retention (compared to Azone(R)) in all three skin models.