A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use

摘要

Context: Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis. Objective: This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability. Materials and methods: Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine. Results: Mean particle size of the terbinafine hydrochloride transfersomes was 69.6?±?1.23?nm, and the entrapment efficiency was 95.4%?±?0.51. The content of the gel was 4.45?±?0.15?mg/g. The accumulated permeation of the transfersomes gel in 12?h was 88.52?±?4.06?μg?cm?2 and the intracutaneous drug detention was 94.38?±?5.26?μg?cm–2. The results of pharmacokinetic studies showed the C_max and area under the curve (AUC) were apparently higher than the commercial cream. Discussion and conclusion: The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.