OBJECTIVES: The poor success rate of topical therapy in nail disorders is mainly because of the low permeability of keratinized nail plates. This can be overcome by utilizing potent perungual drug penetration enhancers that facilitate the drug permeation across the nail plate. This study evaluated the efficacy of inorganic salts in enhancing the trans-nail permeation using a model potent antifungal agent, terbinafine hydrochloride. METHODS: Permeation studies were carried out across human cadaver nail in a Franz diffusion cell using terbinafine solution (1 mg/ml; pH 3). Preliminary studies were carried out to assess the effect of salts (0.5 M) on the terbinafine permeation into and through the nail. Further, the influence of salt concentration (0.25-3 M) on permeation, the mechanism for the enhancement and the suitability of developing a formulation were also studied. KEY FINDINGS: Terbinafine permeation (3-5 fold) through the nail and drug load (4-7 fold) in the nail were enhanced significantly when salts were used at 0.5 M concentration. Increase in salt concentration up to 1 M increased the permeation, which decreased with further increase in salt concentration (>1 M). Mechanistic studies revealed that the enhanced permeation by salts was mainly due to their ability to increase the nail hydration and also to increase the thermodynamic activity of the drug. The cumulative amount of terbinafine permeated at 24 h from the formulated gel (9.70 +/- 0.93 microg/cm(2)) was comparable with that of a solution (11.45 +/- 1.62 microg/cm(2)). CONCLUSIONS: Given the promising results from the permeation and drug load studies, it was concluded that inorganic salts could be used as potent transungual permeation enhancers.
OBJECTIVES: The poor success rate of topical therapy in nail disorders is mainly because of the low permeability of keratinized nail plates. This can be overcome by utilizing potent perungual drug penetration enhancers that facilitate the drug permeation across the nail plate. This study evaluated the efficacy of inorganic salts in enhancing the trans-nail permeation using a model potent antifungal agent, terbinafine hydrochloride. METHODS: Permeation studies were carried out across human cadaver nail in a Franz diffusion cell using terbinafine solution (1 mg/ml; pH 3). Preliminary studies were carried out to assess the effect of salts (0.5 M) on the terbinafine permeation into and through the nail. Further, the influence of salt concentration (0.25-3 M) on permeation, the mechanism for the enhancement and the suitability of developing a formulation were also studied. KEY FINDINGS:Terbinafine permeation (3-5 fold) through the nail and drug load (4-7 fold) in the nail were enhanced significantly when salts were used at 0.5 M concentration. Increase in salt concentration up to 1 M increased the permeation, which decreased with further increase in salt concentration (>1 M). Mechanistic studies revealed that the enhanced permeation by salts was mainly due to their ability to increase the nail hydration and also to increase the thermodynamic activity of the drug. The cumulative amount of terbinafine permeated at 24 h from the formulated gel (9.70 +/- 0.93 microg/cm(2)) was comparable with that of a solution (11.45 +/- 1.62 microg/cm(2)). CONCLUSIONS: Given the promising results from the permeation and drug load studies, it was concluded that inorganic salts could be used as potent transungual permeation enhancers.
Authors: Elena Cutrín-Gómez; Soledad Anguiano-Igea; M Begoña Delgado-Charro; José Luis Gómez-Amoza; Francisco J Otero-Espinar Journal: Pharmaceutics Date: 2018-09-11 Impact factor: 6.321