盐酸特比萘芬生物黏附性成膜凝胶的制备及其体外评价

Preparation and in vitro evaluation of a new terbinafine hydrochloride bioadhesive film-forming gel

以盐酸特比萘芬为模型药物,制备一种生物黏附性成膜凝胶,测定其理化性质。其黏度为(13299±51)mPa·s,pH为3.50±0.50,凝胶剪切黏度为(196±4)g/cm^2;膜固体剩余率为(50.74±2.81)%,膜拉伸强度为(1.17±0.21)MPa,膜断裂伸长率为(21.42±3.24)%。采用《中华人民共和国药典》(2010年版)桨碟法测定其体外释放度,并绘制释放曲线,结果表明,药物在体外能够维持10h的平稳释放;以小香猪皮为透皮屏障,采用改良的Franz扩散池法进行体外透皮释放研究,结果表明,药物不透过皮肤,局部用药安全,其中(93.05±5.66)%的药物滞留于皮肤表面,(1.15±0.85)%进入皮肤内,有利于浅表性皮肤真菌感染的治疗。

The aim of this study was to conduct the preparation and pharmaceutical characterization of a new type of terbinafine hydrochloride bioadhesive film-forming gel. The viscosity of the gel of （13 299 ±51） mPa-s, pH of 3.50 ± 0.50, and the shearing viscosity of （ 196 ± 4） g,/cm2 was found. This new gel turned out to be a layer of solid film on the application site in a very short time. The remaining solid ratio of the resulting film was estimated to be （50.74 ± 2.81） %;the tensile strength was （1.17 ±0.21） MPa; and the breaking elongation was （21.42 ± 3. 24）%. In vitro release behavior of terbinafine hydrochloride from the film was investigated according to the paddle over disk method in ChP2010. Terbinafine hydrochloride released continuously for 10 h from the film. Improved Franz type diffusion cells were used in vitro transdermal studies by the application of excised minipigs skins. No penetration of drug into the receptor medium across the skin existed and so it could imply the safety for local application. It was found that （ 93.05± 5.66） % of drug stayed on the skin surface while （ 1.15 ± 0.85） % entered into the skin, which was beneficial for the treatment of superficial skin fungal infection.