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Formulation strategies for dermal delivery of angiotensin converting enzyme inhibitors

Helal, Fouad; (2020) Formulation strategies for dermal delivery of angiotensin converting enzyme inhibitors. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Each year, a large number of people develop scars all over the world as a result of abnormal wound healing. However, the current treatment strategies available have demonstrated insufficient outcomes and limitations. Even though studies have shown that angiotensin converting enzyme inhibitors (ACEIs) can be a cutting edge scar treatment, licensed topical formulations of ACEIs have not been yet available for use. Therefore, an attempt has been made in the present work to design stable topical formulations of ACEIs and evaluate the percutaneous absorption of the drugs across porcine ear skin as a surrogate model of human skin. Since the quality of any formulation relies on its stability and efficacy, three different ACEIs, moexipril (MOX), ramipril (RAM), and cilazapril (CILA), were underwent stability studies at 32 ˚C in a wide range of dermal vehicles. Among these three compounds, CILA exhibited good stability while the others were degraded under the experimental conditions resulting in diketopiperazine formation. Based on the findings of the stability studies, simple and complex topical formulations of CILA were developed. The permeation data demonstrated the feasibility of dermal delivery of CILA across porcine skin. Furthermore, the results indicated that the complexity of the topical formulation had a pronounced effect on the permeation rate. The hydrolysed form of CILA, cilazaprilat, was also found in the receptor phase, indicating that CILA may undergo metabolism during the permeation. This was confirmed by evaluating the susceptibility of CILA to metabolism by porcine skin homogenate. Overall, the findings indicated that CILA was extensively metabolized by skin esterases leading to metabolite formation, specifically, cilazaprilat. We reported for the first time the possibility of the topical delivery of cilazapril. Ultimately, the work described here will lead to the design and development of new and better topical formulations for the management of wounds.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Formulation strategies for dermal delivery of angiotensin converting enzyme inhibitors
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
URI: https://discovery.ucl.ac.uk/id/eprint/10096644
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