米诺地尔搽剂体外透皮一致性研究

Study on in vitro transdermal consistency of minoxidil solution

目的:比较5%米诺地尔搽剂试验制剂和参比制剂透皮作用的一致性。方法:以巴马香猪皮肤作为透皮渗透的材料,选用立式改良Franz扩散池测定米诺地尔搽剂的渗透规律,采用液相色谱-串联质谱法(LC-MS/MS)分别测定接收液中药物的渗透总量和猪皮中药物的滞留量随时间的变化关系。结果:试验制剂和参比制剂在巴马香猪皮肤中24 h米诺地尔的累积渗透量分别为(49 721±29 707) ng·cm^(–2)和(45 372±23 755) ng·cm^(–2);平均渗透速率分别为(2 352±1 309) ng·cm^(–2)·h^(–1)和(2 182±1 080) ng·cm^(–2)·h^(–1);皮肤滞留量分别为(218 276±137 675) ng·g^(–1)和(188 040±49 523) ng·g^(–1);试验制剂与参比制剂在累积渗透量约为总透过量一半时(12 h)的平均渗透速率分别为(2 172±1 330) ng·cm^(–2)·h^(–1)和(1 947±1 037) ng·cm^(–2)·h^(–1)。结论:5%米诺地尔搽剂试验制剂与参比制剂的透皮渗透程度和速率符合外用制剂的一致性要求,且在猪皮内药物滞留特征相似。

OBJECTIVE To compare the consistency of transdermal effect of 5% minoxidil solution test product versus reference product. METHODS Bama miniature pig skin was utilized as a material for transdermal penetration and vertical modified Franz diffusion cell for determining the penetration of minoxidil solution. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was employed for determining the relationship between total amount of drug permeation in receiving solution and retention of drug in skin with time. RESULTS Test and reference products in skin for 24 h cumulative permeation were (49 721±29 707) and (45 372±23 755) ng·cm^(–2);Average permeation rates were (2 352±1 309) and (2 182±1 080) ng·cm^(–2)·h^(–1);24 h skin retention (218 276±137 675) and (188 040±49 523) ng·g^(–1);Average permeation rates of test and reference products at a cumulative permeation of about half total permeation (12 h) were (2 172±1 330) and (1 947±1 037) ng·cm^(–2)·h^(–1). CONCLUSION Degree and rate of transdermal penetration of 5% minoxidil solution test/reference formulation fulfill the consistency requirements for topical formulations. And drug retention characteristics of minoxidil solution are similar in Bama miniature pig skin.