Investigation of binary and ternary solvent systems for dermal delivery of methadone.

Methadone appears to be a promising candidate for pain management. Previously, we conducted a comprehensive characterization study of methadone base and evaluated the dermal delivery of methadone from various neat solvents. Four solvents, namely d-limonene (LIM), ethyl oleate (EO), Transcutol® P (TC) and octyl salicylate (OSAL), were identified as the optimal neat solvents for skin delivery of the compound. To explore further approaches to improve methadone permeation, the present work investigated a range of binary and ternary vehicles. In vitro permeation studies in porcine skin confirmed that binary systems delivered significantly higher (p < 0.05) amounts of methadone through the skin compared with neat solvents. The highest skin permeation was observed for formulations composed of propylene glycol (PG) and TC. Nine formulations were subsequently examined in human skin. A good correlation (r2 = 0.80) for methadone permeation was obtained between porcine ear skin and human skin data. Solvent uptake studies indicated that the presence of PG not only increased methadone permeation but also TC permeation. The drug appears to "track" the permeation of TC. Future studies will expand further the range of potential vehicles for optimal delivery of the drug, that will ultimately to be investigated in clinical studies.