Au Wai Ling, Skinner Michael, Kanfer Isadore
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa.
J Pharm Pharm Sci. 2008;11(1):160-6. doi: 10.18433/j3np48.
The assessment of the degree of skin blanching following the application of a formulation containing a topical corticosteroid has been established as a surrogate method for the determination of bioequivalence. In this study, both visual and chromametric assessments have been carried out on two topical creams containing clobetasol propionate (0.05%) and the results from both methods are compared.
Human subjects (volunteers) were screened using a cream containing 0.05%clobetasol propionate, in order to identify appropriate subjects for inclusion in the study. The study was implemented according to the FDA guidance using both visual and chromameter assessment techniques. Blanching responses were assessed visually by three trained, independent observers and instrumentally using a Chromameter. An ED50 of 36 min was used as the dose duration based upon data previously obtained from a pilot study using the same topical corticosteroid reference product. A visual rating scale of 0-4 and the a-scale readings from the chromameter were used.
The visual and chromameter blanching profiles showed similar blanching responses with good correspondence. The 90% confidence intervals for the data from both methods were calculated using Locke's method. When only the data obtained from 23 subjects who were identified as"detectors" (as per FDA guidance) were used, the products fell within the bioequivalence acceptance range of 80-125% using the visual assessment method (99.3-111.6%) whereas the data using a chromameter (86.5-129.3%) were just outside the acceptance limits. However, when all subjects (n=34) were included in the calculations, both the visual (97.9-109.2) and chromameter (90.2-120.7) data fell within the bioequivalence acceptance range.
Whereas visual data indicated bioequivalence using either data from "detectors" or data from all subjects, the chromameter data from "detectors" only indicated bioinequivalence but inclusion of all subject data fell within the acceptance range to be declared bioequivalent.
使用含有局部用皮质类固醇的制剂后皮肤变白程度的评估已被确立为生物等效性测定的替代方法。在本研究中，对两种含丙酸氯倍他索（0.05%）的外用乳膏进行了视觉和色度测定评估，并比较了两种方法的结果。
使用含0.05%丙酸氯倍他索的乳膏对人类受试者（志愿者）进行筛选，以确定适合纳入研究的受试者。该研究按照美国食品药品监督管理局（FDA）的指南实施，采用视觉和色度计评估技术。由三名经过培训的独立观察者对变白反应进行视觉评估，并使用色度计进行仪器测量。根据先前使用相同局部用皮质类固醇参比产品的预试验获得的数据，将36分钟的半数有效剂量（ED50）用作剂量持续时间。使用0 - 4的视觉评分量表和色度计的a值读数。
视觉和色度计变白曲线显示出相似的变白反应，具有良好的一致性。使用洛克方法计算了两种方法数据的90%置信区间。当仅使用根据FDA指南被确定为“检测者”的23名受试者的数据时，使用视觉评估方法（99.3 - 111.6%），产品落在生物等效性接受范围80 - 125%内，而使用色度计的数据（86.5 - 129.3%）刚好超出接受限度。然而，当所有受试者（n = 34）纳入计算时，视觉（97.9 - 109.2）和色度计（90.2 - 120.7）数据均落在生物等效性接受范围内。
虽然视觉数据表明使用“检测者”的数据或所有受试者的数据均具有生物等效性，但仅“检测者”的色度计数据表明生物不等效，但纳入所有受试者的数据落在接受范围内，可宣布为生物等效。
