Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica.

AIM: The purpose of this study was to evaluate skin permeation and penetration of nonivamide which has been formulated in novel film-forming formulations (FFFs). These formulations aim to prolong the availability of capsaicinoids which are used in long-term treatment of chronic pruritus. METHODS: An oily solution of nonivamide was loaded into porous silica particles which then were suspended in an aqueous dispersion of a sustained release polymer. Permeation and penetration experiments were performed ex vivo with postauricular porcine skin using modified Franz diffusion cells. The penetrated drug amount was assessed ex vivo by skin surface biopsy followed by cryo-sectioning. Furthermore, in vivo skin irritation experiments were performed to compare the potential skin irritation caused by the FFFs to conventionally used semi-solid formulations. RESULTS: Permeation rates of nonivamide from FFF through the skin are comparable to that from clinically used immediate release formulations. This elucidates the therapeutic safety profile of the novel FFF. Penetration studies confirmed the prolonged drug availability at the site of action. FFFs were found not to irritate the skin of healthy volunteers. CONCLUSION: FFFs with sustained nonivamide penetration represent safe and easy-to-use formulations. They therefore may improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance through a sustained release regime.

Film-forming formulations containing porous silica for the sustained delivery of actives to the skin.

The purpose of this study was to develop film-forming formulations facilitating long-term treatment of chronic pruritus with capsaicinoids. To this end, an oily solution of nonivamide was loaded into porous silica particles which were then suspended in the dispersion of a sustained release polymer. Such formulations form a film when applied to the skin and encapsulate the drug loaded silica particles in a dry polymeric matrix. Dermal delivery and permeation of the antipruritic drug nonivamide (NVA) are controlled by the matrix. The film-forming formulations were examined regarding homogeneity, storage stability, substantivity and ex vivo skin permeation. Confocal Raman spectral imaging proved the stability of silica-based film-forming formulations over a period of 6 months. Substantivity was found to be enhanced substantially compared to a conventional semisolid formulation. Permeation rates of nonivamide from film-forming formulations through the skin are much lower compared to those achieved with a conventional immediate release formulation with the same drug amount. Due to the drug reservoir in the polymer matrix, a sustained permeation is enabled. Film-forming formulations may therefore improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance through a sustained release regime.