Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation

Pharmaceuticals

Josefa Badia¹  MaríaJ. Rodríguez-Lagunas¹  Natalia Díaz-Garrido¹  María-José Fábrega²  AnaCristina Calpena³  LupeCarolina Espinoza³  Paulo Sarango-Granda³  Marcelle Silva-Abreu³  Lyda Halbaut³ 

[1] Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain;Department of Experimental and Health Sciences, Parc de Recerca Biomèdica de Barcelona. University Pompeu Fabra (UPF), 08005 Barcelona, Spain;Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain;

关键词: apremilast;    phosphodiesterase 4;    microemulsion;    skin diseases;    inflammation;   

DOI  :  10.3390/ph13120484

来源: DOAJ

【 摘 要 】

Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.

【 授权许可】

Unknown