Diba Abdollahi1, Zahra Jafariazar1, Minoo Afshar1. 1. Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Abstract
BACKGROUND: Onychomycosis, a fungal nail infection, is an important problem as it may cause local pain, paresthesia, difficulties in performing activities of daily life, and impair social interactions. Systemic treatment of onychomycosis presents safety issues due to possible drug-drug interactions and severe side effects. Although topical therapy of onychomycosis is advantageous due to its localized effect, the efficacy of such therapy depends on achieving effective concentrations of antifungal agents at the infection site. An approach to reach to this end would be driving benefit from synergic activity of antifungal agents for example itraconazole and monoterpenes. However, because of low transungual penetration of itraconazole, a molecule with high molecular weight and very low water-solubility, the effect of the latter compounds on itraconazole nail delivery should be investigated, which was the aim of this study. METHODS: Ex vivo permeation experiments were carried out through soaking the nail clippings of ten healthy volunteers in control and working solutions containing itraconazole (1 mg mL-1 ) and itraconazole (1 mg mL-1 ) plus 6% of each monoterpene including camphor, eucalyptol, menthol, and thymol, respectively, for 36 hours. The amount of itraconazole in nail clippings was quantified hereafter using a validated HPLC method. RESULTS: Statistical analysis showed that itraconazole transungual permeation was not influenced by the studied monoterpenes (P value > .05). CONCLUSION: These results provided a new perspective for designing topical dosage forms for the treatment of onychomycosis.
BACKGROUND:Onychomycosis, a fungal nail infection, is an important problem as it may cause local pain, paresthesia, difficulties in performing activities of daily life, and impair social interactions. Systemic treatment of onychomycosis presents safety issues due to possible drug-drug interactions and severe side effects. Although topical therapy of onychomycosis is advantageous due to its localized effect, the efficacy of such therapy depends on achieving effective concentrations of antifungal agents at the infection site. An approach to reach to this end would be driving benefit from synergic activity of antifungal agents for example itraconazole and monoterpenes. However, because of low transungual penetration of itraconazole, a molecule with high molecular weight and very low water-solubility, the effect of the latter compounds on itraconazole nail delivery should be investigated, which was the aim of this study. METHODS: Ex vivo permeation experiments were carried out through soaking the nail clippings of ten healthy volunteers in control and working solutions containing itraconazole (1 mg mL-1 ) and itraconazole (1 mg mL-1 ) plus 6% of each monoterpene including camphor, eucalyptol, menthol, and thymol, respectively, for 36 hours. The amount of itraconazole in nail clippings was quantified hereafter using a validated HPLC method. RESULTS: Statistical analysis showed that itraconazole transungual permeation was not influenced by the studied monoterpenes (P value > .05). CONCLUSION: These results provided a new perspective for designing topical dosage forms for the treatment of onychomycosis.