Iliopoulos, Fotis; (2021) Investigation of topical delivery of two model hydrophilic compounds. Doctoral thesis (Ph.D), UCL (University College London).

Abstract

Human skin is a remarkably good barrier to the absorption of topically applied substances. Dermal formulations have been widely used for cosmetic or medical purposes; however, the majority of products deliver only a few percent of the active to the skin and therefore they have limited therapeutic benefits. The aim of the present study was to rationally design topical formulations for optimal delivery of two model hydrophilic actives: 3-O-ethyl-l-ascorbic acid (EA) and niacinamide (NIA). EA is an ether derivative of vitamin C, and has been used as a skin-lightening agent to treat skin pigmentation disorders. NIA is the amide form of vitamin B3 and it is used as a topical treatment for conditions such as atopic dermatitis, rosacea, and inflammatory acne. These compounds are widely found in marketed products. However, to date, there is no information on the ability of EA to permeate the skin, while only limited data exist on NIA delivery following clinically relevant doses. In this study, a comprehensive characterisation of the model compounds was undertaken, including thermal analysis, partition coefficient determination, stability and solubility studies. The in vitro performance of formulations was evaluated by Franz diffusion and mass balance studies in porcine and human skin under finite dose conditions. The actives were formulated as single solvent systems, and subsequently more complex vehicles were investigated for their potential for synergistic enhancement of skin delivery. Vehicles comprising propylene glycol and the fatty acid esters propylene glycol monolaurate and isopropyl myristate showed the greatest penetration enhancement for both EA and NIA. Finally, in vivo studies using tape-stripping were performed on human subjects to determine the effects of selected vehicles on the delivery of the actives under real-life conditions. Overall, the present work demonstrated that rational selection of vehicles significantly enhanced percutaneous absorption of hydrophilic actives with the promise of improved efficacy of topical formulations.

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