Sherif, Solomon; (2024) Rational Formulation Design of Topical Tazarotene a Third-Generation Retinoid. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The skin acts as an essential barrier to the outside world through a complex structure of lipids and proteins making topical drug delivery a major challenge for formulation scientists. Retinoids are compounds that provide therapeutic benefits for a range of dermatological conditions by actioning on the retinoic acid receptor (RAR). First- and second-generation retinoids however are associated with unwanted side effects as a consequence of indiscriminate RAR targeting. Tazarotene was developed as a third-generation selective retinoid binding predominantly to the RAR-Ƴ subunit, which is the primary target of retinoid therapy to increase efficiency and reduce the severity of or eliminate unwanted side effects. The lipophilic nature of tazarotene however prevents it from effectively penetrating the skin to exert its full effects. In this thesis, the physicochemical properties of tazarotene in a range of CPEs were characterised before using them to study the delivery of tazarotene into the skin both in-vitro and in-vivo. Franz diffusion cell studies were conducted with single solvents and a combination of binary or ternary solvent systems. Tape stripping of human volunteers using the best-performing formulations was performed. A novel Confocal Raman Spectroscopy (CRS) technique was used to non-invasively quantify tazarotene and detect CPE deposition in the skin.

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