Paz-Alvarez, Miguel;
(2019)
Mechanistic study of antifungal active ingredients for topical delivery.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Dandruff and its more severe form, seborrheic dermatitis, is a condition affecting a high proportion of the population at some point in their life. Given its cosmetic aspects, focus has been traditionally placed on the clinical improvement of the condition. However, limited research has been aimed at investigating the interaction of antifungals and excipients with the skin. The work presented in this thesis focuses on the development of experimental formulations for the treatment of dandruff based on the skin uptake of active ingredients and the role of excipients in the formulation. After the physicochemical characterisation of climbazole (CBZ) and piroctone olamine (OPX) as model antifungal agents, the effects of dosing and surrogate selection for in vitro models was investigated, showing the relevance of a rational selection of solvents and conditions for in vitro testing. Furthermore, the evaluation of complex formulations in porcine and human abdominal skin were also tested in human scalp and compared to a commercial formulation, where a significant improvement in skin uptake was achieved and the ability of porcine skin to predict the behaviour of human scalp was demonstrated. Pivotal formulation studies were conducted for the combination of OPX and CBZ which were integrated in a single formulation, achieving a high rate of skin permeation comparable to the individual application of each active ingredient. A number of selected formulations were also tested in vivo by means of tape striping and confocal Raman spectroscopy, showing the superiority of binary combinations in terms of skin active deposition and solvent permeation. The combination of both techniques provided a great understanding regarding the role of solvents for the development of efficient formulations for the treatment of dandruff.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Mechanistic study of antifungal active ingredients for topical delivery |
| Event: | UCL |
| Language: | English |
| 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/10086368 |
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