Purpose

The in vitro permeation test (IVPT) with a new statistical approach was investigated to evaluate the utility of an IVPT methodology as a sensitive tool to support a demonstration of bioequivalence (BE) for topical dermatological drug products.

Methods

IVPT experiments were performed utilizing ex vivo human skin. The initial screening tests involved four differently formulated acyclovir 5% creams: the U.S. Zovirax® as the reference product and the U.K. Zovirax®, Aciclovir 1A Pharma® and Aciclostad® as test products. Subsequently, a pivotal BE study was conducted comparing the two Zovirax® creams. The resulting data was used to evaluate BE of test (T) versus reference (R), T versus T, and R versus R, with an adaption of scaled average BE approach to address high variability in IVPT data.

Results

More acyclovir permeated into and through the skin from the two Zovirax® creams compared to the two non-Zovirax® creams. The U.S. Zovirax® cream showed a significantly higher J_max and total amount permeated over 48 h, compared to the U.K. Zovirax® cream. The statistical analysis indicated that the test and reference products were not bioequivalent, whereas each product tested against itself was shown to be bioequivalent.

Conclusions

The current study demonstrated that the IVPT method, with an appropriate statistical analysis of the results, is a sensitive and discriminating test that can detect differences in the rate and extent of acyclovir bioavailability in the skin from differently formulated cream products.

中文翻译：

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阿昔洛韦乳膏 5% 产品的皮肤药代动力学：通过体外渗透试验和比例平均生物等效性的适应评估生物等效性

目的

在体外渗透测试（IVPT）用新的统计方法进行了研究，以评估的IVPT方法的效用作为一个敏感的工具，以支持生物等效性（BE）局部皮肤药产品的演示。

方法

IVPT 实验是利用离体人类皮肤进行的。最初的筛选测试涉及四种不同配方的阿昔洛韦 5% 乳膏：美国 Zovirax® 作为参考产品，英国 Zovirax®、阿昔洛韦 1A Pharma® 和 Aciclostad® 作为测试产品。随后，进行了一项关键的 BE 研究，比较了两种 Zovirax® 乳膏。所得数据用于评估测试 (T) 与参考 (R)、T 与 T 以及 R 与 R 的 BE，并采用缩放平均 BE 方法来解决 IVPT 数据的高可变性。

结果

与两种非 Zovirax® 乳膏相比，两种 Zovirax® 乳膏更多地渗透到皮肤中并通过皮肤。与英国 Zovirax® 乳膏相比，美国 Zovirax® 乳膏在 48 小时内表现出显着更高的 J _max和渗透总量。统计分析表明，受试产品和参比产品不具有生物等效性，而针对自身进行测试的每种产品均显示为生物等效性。

结论

目前的研究表明，IVPT 方法对结果进行了适当的统计分析，是一种敏感和有区别的测试，可以检测不同配方乳霜产品在皮肤中阿昔洛韦生物利用度的速率和程度的差异。