eprintid: 10100259 rev_number: 22 eprint_status: archive userid: 608 dir: disk0/10/10/02/59 datestamp: 2020-06-11 11:33:12 lastmod: 2021-10-11 22:24:18 status_changed: 2020-06-11 11:33:12 type: article metadata_visibility: show creators_name: Lane, M creators_name: Kung, C-P creators_name: Hadgraft, J creators_name: Zhang, Y creators_name: Sil, B creators_name: Patel, B creators_name: McCulloch, R title: Investigation of binary and ternary solvent systems for dermal delivery of methadone ispublished: pub subjects: GOSH divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G08 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: 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. date: 2020-08-30 date_type: published publisher: Elsevier official_url: https://doi.org/10.1016/j.ijpharm.2020.119538 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1788610 doi: 10.1016/j.ijpharm.2020.119538 lyricists_name: Hadgraft, Jonathan lyricists_name: Lane, Majella lyricists_name: Zhang, Yanling lyricists_id: JHADR30 lyricists_id: MLANE69 lyricists_id: YZHAH96 actors_name: Lane, Majella actors_id: MLANE69 actors_role: owner full_text_status: public publication: International Journal of Pharmaceutics volume: 586 article_number: 119538 citation: Lane, M; Kung, C-P; Hadgraft, J; Zhang, Y; Sil, B; Patel, B; McCulloch, R; (2020) Investigation of binary and ternary solvent systems for dermal delivery of methadone. International Journal of Pharmaceutics , 586 , Article 119538. 10.1016/j.ijpharm.2020.119538 <https://doi.org/10.1016/j.ijpharm.2020.119538>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10100259/1/Methdone%202nd%20paper.pdf