Basic Sciences Research Center, KLE University, Belgaum, Karnataka, 590010, India.
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, 6139, South Africa.
AAPS PharmSciTech. 2018 May;19(4):1567-1573. doi: 10.1208/s12249-018-0971-x. Epub 2018 Feb 26.
This study indicates the application of tape stripping (TS) for bioequivalence (BE) assessment of a topical cream product containing 5% acyclovir. A TS method, previously used successfully to assess BE of topical clobetasol propionate and clotrimazole formulations, was used to assess BE of an acyclovir cream (5%) formulation as well as a diluted acyclovir formulation (1.5%) applied to the skin of healthy humans. An appropriate application time was established by conducting a dose duration study using the innovator product, Zovirax® cream. Transepidermal water loss was measured and used to normalize thicknesses between subjects. The area under the curve (AUC) from a plot of amount of acyclovir/strip vs cumulative fraction of stratum corneum (SC) removed was calculated for each application site. BE was assessed using Fieller's theorem in accordance with FDA's guidance for assessment of BE of topical corticosteroids. Adco-acyclovir cream (5%) was found to be BE to Zovirax® cream, where the mean test/reference (T/R) ratio of the AUC's was 0.96 and the bioequivalence interval using a 90% confidence interval was 0.91-1.01 with a statistical power > 95%, whereas the diluted test product fell outside the BE acceptance criteria with T/R ratio of AUC of 0.23 and a 90% CI of 0.20-0.26. This study indicates that the data resulting from the application of this TS procedure has reinforced the potential for its use to assess BE of topical drug products intended for local action, thereby obviating the necessity to undertake clinical trials in patients.
本研究表明，胶带剥落（TS）可用于评估含有 5%阿昔洛韦的局部乳膏产品的生物等效性（BE）。先前成功用于评估局部丙酸氯倍他索和克霉唑制剂 BE 的 TS 方法，也用于评估阿昔洛韦乳膏（5%）制剂和局部应用于健康人体的稀释阿昔洛韦制剂（1.5%）的 BE。通过使用创新产品 Zovirax®乳膏进行剂量持续时间研究确定了适当的应用时间。测量经皮水分损失并用于在受试者之间归一化厚度。从阿昔洛韦/条的量与累积角质层（SC）去除分数的曲线下面积（AUC）的图中计算每个应用部位的 AUC。根据 FDA 关于评估局部皮质类固醇 BE 的指南，使用 Fieller 定理评估 BE。Adco-acyclovir 乳膏（5%）被发现与 Zovirax®乳膏具有 BE，其中 AUC 的平均测试/参考（T/R）比值为 0.96，使用 90%置信区间的生物等效区间为 0.91-1.01，统计功效>95%，而稀释的测试产品的 AUC 的 T/R 比值为 0.23，90%CI 为 0.20-0.26，超出了 BE 接受标准。这项研究表明，应用这种 TS 程序所产生的数据增强了其用于评估局部作用的局部药物产品的 BE 的潜力，从而避免了在患者中进行临床试验的必要性。
