Postdoctoral Fellow, Biopharmaceutics Research Institute, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
Research Officer, Biopharmaceutics Research Institute, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
J Pharm Pharm Sci. 2020;23:437-450. doi: 10.18433/jpps31534.
The main aim of the current research was to develop and apply a dermatopharmacokinetic (DPK) approach for the bioequivalence assessment of metronidazole (MTZ) topical cream products, indicated in the treatment of rosacea.
A DPK methodology using tape stripping (TS) technique was developed by investigating the factors that may influence the TS results viz. tapes, dose durations, number of tapes to be used, pressure application, dose applied and gravimetric analysis of the tapes. An initial dose duration study was performed on 6 healthy participants to determine an appropriate application time duration using the Emax model. The SC thickness was normalised between participants using TEWL measurements. A pivotal study was conducted using both the arms of 10 healthy human participants to demonstrate the ability of the TS method for bioequivalence assessment by comparing the reference product to itself as a positive control and including products with higher and lower strengths of MTZ to serve as negative controls in order to confirm bioinequivalence.
Whereas the reference was found to be bioequivalent when compared to itself, the creams containing 0.56% and 0.95% MTZ (negative controls) were not bioequivalent (bioinequivalent). Furthermore, another product containing 0.75% MTZ was also assessed and was found to be bioequivalent to the reference product. In addition, the use of both forearms of each participant offered an important advantage of significantly reducing the number of human subjects required to demonstrate BE with a high statistical power of > 80%.
The data obtained provides compelling evidence that the developed TS method has the potential to be a cost-effective surrogate alternative for lengthy and expensive clinical trials. Consequently, its application can facilitate faster development of generic products which would, in turn, lower the economic burden of healthcare.
本研究的主要目的是开发和应用一种皮肤药代动力学（DPK）方法，用于评估米诺环素（MTZ）外用乳膏产品的生物等效性，这些产品用于治疗酒渣鼻。
通过研究可能影响胶带技术（TS）结果的因素，开发了一种 DPK 方法，这些因素包括胶带、剂量持续时间、使用的胶带数量、压力应用、应用剂量和胶带的重量分析。在 6 名健康参与者中进行了初步的剂量持续时间研究，使用 Emax 模型确定合适的应用时间持续时间。使用 TEWL 测量值对参与者之间的 SC 厚度进行归一化。使用 10 名健康人类参与者的双臂进行了关键性研究，通过将参考产品与其自身进行比较，证明了 TS 方法用于生物等效性评估的能力，并将含有更高和更低浓度 MTZ 的产品作为阴性对照，以确认生物不等效性。
参考产品与自身相比被发现是生物等效的，而含有 0.56%和 0.95% MTZ（阴性对照）的乳膏则不是生物等效的（生物不等效）。此外，还评估了另一种含有 0.75% MTZ 的产品，发现其与参考产品具有生物等效性。此外，每个参与者的两个前臂的使用提供了一个重要的优势，可以显著减少证明 BE 所需的人类受试者数量，具有 >80%的高统计功效。
获得的数据提供了令人信服的证据，表明开发的 TS 方法具有成为一种经济有效的替代方法的潜力，可以替代漫长而昂贵的临床试验。因此，它的应用可以促进更快速地开发仿制药，从而降低医疗保健的经济负担。
