盐酸特比萘芬脂质体的处方优化及其凝胶剂的透皮行为

Formulation Optimization of Terbinafine Hydrochloride Liposomes and Transdermal Behavior of Gels Loaded with the Liposomes

采用乙醇注入法制备盐酸特比萘芬脂质体。在单因素试验基础上,以包封率为考察指标,采用Box-Behnken设计及响应面法优化了磷脂浓度、磷脂与药物质量比和磷脂与胆固醇质量比。优化后处方为:磷脂浓度10.3 mg/ml,磷脂与药物质量比为21.3∶1,磷脂与胆固醇质量比为9.4∶1。该脂质体包封率可达(87.54±0.59)%。再将该脂质体制成凝胶,考察其经皮渗透行为。结果表明,盐酸特比萘芬凝胶及其脂质体凝胶的24 h累积透皮量为(103.5±11.5)和(133.8±10.4)mg/cm^2,表皮内滞留量为(345.5±22.9)和(678.3±34.1)mg/cm^2,真皮内滞留量为(226.1±18.3)和(323.2±22.6)mg/cm^2。可见,脂质体凝胶的透皮量和皮内滞留量均比普通凝胶显著提高(P<0.05)。

Terbinafine hydrochloride liposomes were prepared by ethanol injection method. Based on the results of single factor experiment, the Box-Behnken experimental design and the response surface method were adopted to optimize the phospholipid concentration, phospholipid-drug weight ratio and phospholipid-cholesterol weight ratio of liposomes with encapsulation efficiency as the index. The optimal formulation was as follows： the phospholipid concentration was 10.3 mg/ml, the phospholipid-drug weight ratio was 21.3 ： 1, and the phospholipid-cholesterol weight ratio was 9.4 ： 1. The encapsulation efficiency of the optimal liposomes was （87.54±0.59） %. Then the gels containing the above liposomes were prepared and the transdermal behavior was also investigated. The results showed that the cumulative amount at 24 h, the drug retention in the epidermis or dermis of the gels containing the bulk drug or the above liposomes were （103.5±11.5） and （133.8±10.4）μg/cm2, （345.5±22.9） and （678.3±34.1）μg/cm2, （226.1± 18.3） and （323.2±22.6）μg/cm2, respectively. Compared with gels loaded with terbinafine hydrochloride, the cumulative amount and retention in skin of gels loaded with the liposomes were significantly increased （P〈0.05）.