Nanoemulsion containing 8-methoxypsoralen for topical treatment of dermatoses: Development, characterization and ex vivo permeation in porcine skin

• Published in: International journal of pharmaceutics 2018-08, Vol.547 (1-2), p.1-9
• Main Authors: Oliveira, Catarina Amorim, Gouvêa, Marcos Martins, Antunes, Gabriel Ramos, Freitas, Zaida Maria Faria de, Marques, Flávia Ferreira de Carvalho, Ricci-Junior, Eduardo
• Format: Article
• Language: English
• Subjects: 8-Methoxypsoralen; Ex vivo permeation; Formulation characterization; HPLC-Fluo; Nanoemulsion
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.05.053

[Display omitted] Oral therapy with 8-methoxypsoralen (8-MOP) may cause major side effects, whereas the topical treatment might not be much effective due to the low penetration induced by typical formulations. Therefore, the objectives of this work are the development and characterization of a nanoemulsion (NE) containing 8-MOP together with an ex vivo permeation study, monitored by a validated HPLC-Fluo method, to determine the amount of drug retained in viable skin (epidermis (E) and dermis (D)) and in stratum corneum (SC). The optimized conditions for NE formulation were achieved by full factorial designs (25 and 32): 60 s and 60% of ultrasound time and potency, respectively; 10 mL of final volume; 2% v/v of oil phase (clove essential oil); and 10% m/v of Poloxamer 407. The NE showed mean droplet diameter of 24.98 ± 0.49 nm, polydispersity index (PDI) of 0.091 ± 0.23, pH values of 6.54 ± 0.06, refractive index of 1.3525 ± 0.0001 and apparent viscosity of 51.15 ± 3.66 mPa at 20 °C. Droplets with nanospherical diameters were also observed by transmission electron microscopy (TEM). Ex vivo permeation study showed that 8.5% of the applied 8-MOP dose permeated through the biological membranes, with flux (J) of 1.35 μg cm−2 h−1. The drug retention in E + D and in SC was 10.15 ± 1.36 and 1.95 ± 0.71 µg cm−2, respectively. Retention in viable skin induced by the NE was almost two-fold higher than a compounded cream (5.04 ± 0.30 μg cm−2). These results suggested that the developed NE is a promising alternative for 8-MOP topical therapy when compared to commercial formulations.