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

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 degrees C and 40 degrees 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. (c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

Topical film-forming solutions (FFSs) have potential for improving dermal delivery by prolonging substantivity, establishing transient supersaturation, and enhancing solubility. This study successfully developed an FFS composed of tazarotene and polyamide-3 polymers, which demonstrated improved skin delivery and stability. The solid solution films significantly increased the glass transition temperature and enhanced tazarotene penetration compared to a commercial cream. Thus, topical solid solutions may offer an option for enhanced dermal API delivery.