Skin pharmacokinetics of diclofenac and co-delivered functional excipients

• Published in: International journal of pharmaceutics 2022-02, Vol.614, p.121469-121469, Article 121469
• Main Authors: Tabosa, M. Alice Maciel, Cordery, Sarah F., Jane White, K.A., Bunge, Annette L., Guy, Richard H., Delgado-Charro, M. Begoña
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Butylene glycol; Diclofenac; Diclofenac - pharmacokinetics; Excipients - pharmacokinetics; Humans; In vivo stratum corneum sampling; Propylene glycol; Skin - metabolism; Skin Absorption; Skin pharmacokinetics; Topical excipients
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.121469

[Display omitted] An important question in the development of a dermatological drug product is whether a target concentration has been achieved in, for example, the viable epidermis following topical administration. When attempting to address this challenge, it is essential to consider the role of excipients in the formulation that may influence drug partitioning and diffusion in the different layers of the skin. The objective, therefore, was to correlate, in human subjects, the skin pharmacokinetics of diclofenac (specifically, its uptake into and clearance from the stratum corneum (SC)) from an approved drug product (Voltaren® medicated plaster) with the in vivo co-uptake of two key excipients, namely propylene glycol and butylene glycol. SC sampling was used to assess diclofenac input into the skin during patch application, and its subsequent clearance post-removal of the delivery system. In parallel the uptake of the two glycol excipients was also measured. Drug and excipient amounts in the SC increased with time of application up to 6 h and, for diclofenac, no further increase was observed when the administration was prolonged to 12 h. When the plaster was removed after 6 h of wear, diclofenac cleared relatively slowly from the SC suggesting that drug binding with a slow off-rate had occurred. The results indicate that the optimisation of drug delivery from a topical formulation must take into account the disposition of key excipients and their impact on dermato-pharmacokinetics in general.