Kung, Chin-Ping;
(2020)
Targeting neuropathic pain with dermal formulations.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The use of amitriptyline and methadone for the management of neuropathic pain has received great interest in recent years. However, serious side effects are often associated with oral administration of these drugs. Emerging evidence has confirmed the peripheral actions of amitriptyline and methadone on pain signalling pathways. Topical/transdermal amitriptyline and methadone have shown efficacy with improved safety profiles in clinical studies. However, little information about their formulations and skin absorption is available. Therefore, the primary objective of the present work was to investigate the dermal delivery of amitriptyline and methadone. Amitriptyline base and methadone base were prepared and selected as the active ingredients in the present work because the free base forms are generally preferred for skin delivery. A novel entity, the amitriptyline-diclofenac ion pair was also synthesized. There is little information about the physicochemical properties of the ion pair, amitriptyline base and methadone base in the literature. Therefore, a series of characterization studies, including thermal analysis, distribution coefficient measurement, stability and solubility studies, were conducted. To evaluate the in vitro performance of dermal formulations, permeation and mass balance studies were conducted in porcine skin and human skin using Franz diffusion cells. Various simple formulations and alcoholic formulations for the amitriptyline-diclofenac ion pair and amitriptyline base were investigated. The use of microemulsions for dermal delivery of amitriptyline base was also evaluated. Various methadone formulations were tested. Formulations containing both propylene glycol and Transcutol® showed the most promising penetration enhancement on methadone base. The skin uptake of solvents was also analysed by gas chromatography and confocal Raman spectroscopy to understand the synergistic actions of propylene glycol and Transcutol® on enhancing methadone permeation. The present work has optimised the dermal formulations of amitriptyline and methadone and provided insights into the mechanisms of various permeation enhancement strategies.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Targeting neuropathic pain with dermal formulations |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10091433 |
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