efinaconazole and Nail-Diseases

Onychomycosis was first described in the mid-1800's, and early treatment regimens involved applying corrosive substances and nail plate avulsion. It was not until the mid-1900's that more specific antifungal agents were utilized. Initially, only oral drugs were used, with ciclopirox 8% solution later approved in 1999. Presently, terbinafine, itraconazole, and fluconazole (off-label) are used for systemic onychomycosis therapy in the US, and topicals include ciclopirox, efinaconazole and tavaborole. Devices, topicals with new mechanisms of action, and oral medications with potentially better efficacy are now being explored for treatment of onychomycosis.

Topics: Administration, Topical; Antifungal Agents; Humans; Itraconazole; Nail Diseases; Onychomycosis; Terbinafine; Triazoles

Efinaconazole is non-lacquer-based with a low surface tension that efficiently targets delivery of active ingredient into the nail and nail bed.. To develop an optimal, stable formulation of efinaconazole topical solution 10% (ETS10).. We evaluated the safety and efficacy of ETS10 on 10 Iranian participants in a pilot, single-group and before-after clinical study, for up to 8 weeks in onychomycosis.. The study showed reasonable results concerning the short period of treatment. During the period of storage, the formulation showed no variation in colour, odour and pH. The average pH at initial, 1st, 6th and 12th months was 4.65, 4.64, 4.65 and 4.64, respectively. The assay of an active pharmaceutical ingredient in the formulation was desired over the whole period. This indicates that antimicrobial activity has been adequate and efficient. A significant decrease in Investigator Global Assessment (IGA) of the target toenails was also defined as the efficacy endpoint. The median score for IGA at baseline visit was 3 out of 5 which decreased to 2 out of 5 and the decrease was statistically significant.. The study clarifies the new efficacy of ETS10 in subjects with onychomycosis and passed the safety study successfully. These properties may develop the potentiality of ETS10 as a good treatment option for patients with onychomycosis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Female; Foot; Humans; Male; Middle Aged; Nail Diseases; Nails; Onychomycosis; Pilot Projects; Triazoles; Young Adult

Topics: Administration, Topical; Aged; Antifungal Agents; Dermatitis, Allergic Contact; Foot Dermatoses; Humans; Male; Nail Diseases; Onychomycosis; Patch Tests; Triazoles

We hypothesised that Hansen Solubility Parameters (HSPs) can be used to predict drug-nail affinities. Our aims were to: (i) determine the HSPs (δD, δP, δH) of the nail plate, the hoof membrane (a model for the nail plate), and of the drugs terbinafine HCl, amorolfine HCl, ciclopirox olamine and efinaconazole, by measuring their swelling/solubility in organic liquids, (ii) predict nail-drug interactions by comparing drug and nail HSPs, and (iii) evaluate the accuracy of these predictions using literature reports of experimentally-determined affinities of these drugs for keratin, the main constituent of the nail plate and hoof. Many solvents caused no change in the mass of nail plates, a few solvents deswelled the nail, while others swelled the nail to varying extents. Fingernail and toenail HSPs were almost the same, while hoof HSPs were similar, except for a slightly lower δP. High nail-terbinafine HCl, nail-amorolfine HCl and nail-ciclopirox olamine affinities, and low nail-efinaconazole affinities were then predicted, and found to accurately match experimental reports of these drugs' affinities to keratin. We therefore propose that drug and nail Hansen Solubility Parameters may be used to predict drug-nail interactions, and that these results can assist in the design of drugs for the treatment of nail diseases, such as onychomycosis and psoriasis. To our knowledge, this is the first report of the application of HSPs in ungual research.

Topics: Adolescent; Adult; Antifungal Agents; Ciclopirox; Drug Interactions; Female; Humans; Keratins; Male; Middle Aged; Morpholines; Nail Diseases; Nails; Naphthalenes; Onychomycosis; Pharmaceutical Preparations; Pyridones; Solubility; Terbinafine; Triazoles; Young Adult

Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate.

Topics: Administration, Topical; Antifungal Agents; Chemistry, Pharmaceutical; Drug Delivery Systems; Foot Dermatoses; Humans; Nail Diseases; Nails; Onychomycosis; Permeability; Pharmaceutical Solutions; Solubility; Triazoles