“…Therefore, a large amount of topically applied hydrophilic CF resides on the skin surface [2] and saturates mainly the outermost SC [29,30]. To solve the problem of permeation through the skin barrier, invasive methods such as microneedling, electroporation, iontophoresis, ultrasound, intradermal injection (including jet injection), and their combination are used to deliver CF into the dermis [31,32]. Alternatively, to provide a transdermal penetration, CF needs to remain in solution, be at a high thermodynamic activity and not crystallize in the SC [2,33], and/or be applied in combination with penetration enhancers [31,34,35], and/or be incorporated in lipophilic vehicle carrier systems, like liposomes [36] or nanoemulsions [32].…”