Topical Film-Forming Solid Solutions for Enhanced Dermal Delivery of the Retinoid Tazarotene

Abstract

Topical film-forming solutions (FFSs) show considerable potential for dermal delivery of an API. Through a mechanism of in situ film formation upon solvent evaporation, they may improve skin delivery by prolonging substantivity on the skin, by establishing a transient supersaturation, and/or by enhancing solubility through the formation of a solid dispersion in the resulting film.This work aimed at developing an FFS for topical application with enhanced skin delivery. The tested FFSs were composed of the lipophilic retinoid tazarotene and the hydrophobic polyamide-3 polymers.The residual films cast from FFSs were examined by DSC and their release mechanism was investigated. Additionally, ex vivo skin penetration of tazarotene was explored.In comparison to a physical mixture, the glass transition (Tg) was significantly increased (p < 0.01) in in-situ generated polyamide-3 (11,500 Da)/tazarotene films with ratios 5:1 and 10:1, indicating a molecular distribution of tazarotene within the polymer. Stress testing at 32°C and 40°C further indicated that these films were kinetically stabilized for at least two weeks. Tazarotene release from solid solution films was notably increased as compared to the crystalline and the amorphous tazarotene. A ten-times higher skin penetration of the ratio 10:1 film (containing 0.1% tazarotene) was observed as compared to a commercial 0.1% tazarotene cream.Hence, topical solid solutions may represent an option for improved dermal API delivery.