Amorolfine HCl

Amorolfine hydrochloride is a antifungal reagent.

In vitro studies with R 51,211 (itraconazole).[Pubmed:6089654]

Antimicrob Agents Chemother. 1984 Jul;26(1):5-9.

The in vitro activity of R 51,211 (itraconazole, accepted generic name; Janssen Pharmaceutica, Beerse, Belgium), a new orally active triazole, was compared with those of two existing orally active azoles, ketoconazole and BAY n 7133, and a topical agent, Ro 14-4767/002. An agar dilution procedure (Kimmig agar) was performed with 148 isolates of pathogenic fungi. Incubation was at 30 degrees C from 48 h to 7 days. R 51,211 was dissolved in 0.2 N HCl in absolute ethanol, ketoconazole was dissolved in 0.2 N HCl alone, BAY n 7133 was dissolved in absolute ethanol, and Ro 14-4767/002 was dissolved in dimethyl sulfoxide. R 51,211 and Ro 14-4767/002 were the most active drugs against isolates of Histoplasma capsulatum, and R 51,211 showed the greatest activity in vitro against isolates of Blastomyces dermatitidis and Cryptococcus neoformans. Ro 14-4767/002 was the most active drug against 30 isolates of dermatophytes, followed by R 51,211, ketoconazole, and BAY n 7133. R 51,211 showed the best activity in vitro against 19 isolates of Aspergillus fumigatus and Aspergillus flavus, as well as 19 isolates of dematiaceous fungi. All four drugs had 90% MICs of greater than or equal to 16 micrograms/ml when tested with isolates of zygomycetous fungi.

Application of Hansen Solubility Parameters to predict drug-nail interactions, which can assist the design of nail medicines.[Pubmed:26924329]

Eur J Pharm Biopharm. 2016 May;102:32-40.

We hypothesised that Hansen Solubility Parameters (HSPs) can be used to predict drug-nail affinities. Our aims were to: (i) determine the HSPs (deltaD, deltaP, deltaH) 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 deltaP. 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.

UV-curable gel formulations: Potential drug carriers for the topical treatment of nail diseases.[Pubmed:26187167]

Int J Pharm. 2015 Aug 15;492(1-2):177-90.

Nail diseases are common, cause significant distress and treatments are far from successful. Our aim was to investigate the potential of UV-curable gels - currently used as cosmetics - as topical drug carriers for their treatment. These formulations have a long residence on the nail, which is expected to increase patient compliance and the success of topical therapy. The gels are composed of the diurethane dimethacrylate, ethyl methacrylate, 2-hydroxy-2-methylpropiophenone, an antifungal drug (Amorolfine HCl or terbinafine HCl) and an organic liquid (ethanol or NMP) as drug solvent. Following its application to a substrate and exposure to a UVA lamp for 2 min, the gel polymerises and forms a smooth, glossy and amorphous film, with negligible levels of residual monomers. No drug-polymer interactions were found and drug loading did not affect the film's properties, such as thickness, crystallinity and transition temperatures. In contrast, the organic solvent did influence the film's properties; NMP-containing films had lower glass transition temperatures, adhesion and water resistance than ethanol-based ones. Water-resistance being a desired property, ethanol-based formulations were investigated further for stability, drug release and ungual permeation. The films were stable under accelerated stability testing conditions. Compared to terbinafine, amorolfine was released to a greater extent, had a higher ungual flux, but a lower concentration in the nailplate. However, both drugs were present at considerably high levels in the nail when their MICs are taken into account. We thus conclude that UV-curable gels are promising candidates as topical nail medicines.