Design and Evaluation of a Self-Adhesive Naproxen-Loaded Film Prepared from a Nanoparticle Dispersion

Abstract

Naproxen-loaded nanoparticles were used to prepare, in a one-step process, unilaminar films of Eudragit E-100 (EE-100), avoiding the use of organic solvents and assuring the homogeneity and molecular dispersion of the drug. Nanoparticle films (NP-F) and conventional films (CV-F, prepared by casting of methanolic solutions onto a Teflon disc) were assayed by their mechanical properties, skin adhesivity, and calorimetric studies to compare their behavior. Different proportions of plasticizer (triacetin) were included to evaluate the quality of the films. Film characterization included in vitro drug release studies through a cellulose membrane using Franz-type cells, and in vivo stratum corneum penetration experiments by the tape stripping technique. The results showed that NP-F were semi-transparent to transparent, suggesting a good compatibility between naproxen and EE-100. Differential calorimetric studies (DSC) confirmed a molecular dispersion of naproxen in the EE-100 matrix. Taking into account the mechanical properties of the films, a 20% triacetin concentration can be considered as optimal for both types of films. The in vitro release data obtained from both systems (NP-F and CV-F) followed the Higuchi's model for matrix systems, with the Fickian diffusion (t(0.5)) being the main release mechanism. Concerning the in vivo penetration studies, no statistical differences were found for the penetrated amount of naproxen across the stratum corneum and the depth of penetration for the two films and between the three contact times (2, 4, and 6 h). The films formulated from nanoparticle dispersions (NP-F) were shown to be effective for the transdermal administration of naproxen, and can be considered as an interesting alternative for the preparation of films with several technological advantages.