Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2022-06-28 , DOI: 10.1007/s13346-022-01186-7 Paige N Zambrana 1 , Dana C Hammell 1 , Audra L Stinchcomb 1
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Due to high variability during clinical pharmacokinetic (PK) evaluation, the prediction of in vivo exposure from in vitro absorption testing of topical semisolid and liquid dermal products has historically proven difficult. Since absorption from unoccluded formulations can be influenced by environmental factors such as temperature and humidity, maximal effort must be placed on the harmonization of experimental parameters between in vitro and in vivo testing conditions to establish accurate in vitro/in vivo correlations (IVIVC). Using four different sunscreen formulations as a model, we performed in vitro permeation testing (IVPT) studies with excised human skin and maintained strict harmonization techniques to control application time, occlusion, temperature, and humidity during in vivo human serum PK evaluation. The goal was to investigate if increased control over experimental parameters would result in decreased inter-subject variability of common topical formulations leading to acceptable IVIVC establishment. Using a deconvolution-based approach, excellent point-to-point (Level A correlation) IVIVC for the entire 12-h study duration was achieved for all four sunscreen formulations with < 10% prediction error of both area under the curve (AUC) and peak concentration (Cmax) estimation. The low variability of in vivo absorption data presents a proof-of-concept protocol design for testing of complex semisolid and liquid topical formulations applied over a large surface area with reapplication in a reliable manner. This work also presents the opportunity for expanded development of testing for the impact of altered temperature and humidity conditions on product absorption in vivo with a high degree of precision.
Graphical abstract
中文翻译：
先进的协调技术可准确建立四种复杂皮肤制剂中氧苯酮的体外-体内相关性并重新应用
由于临床药代动力学 (PK) 评估过程中的高度可变性，从历史上证明，通过局部半固体和液体皮肤产品的体外吸收测试来预测体内暴露是困难的。由于未封闭制剂的吸收会受到温度和湿度等环境因素的影响，因此必须尽最大努力协调体外和体内测试条件之间的实验参数，以建立准确的体外/体内相关性 (IVIVC)。我们使用四种不同的防晒配方作为模型，对切除的人体皮肤进行了体外渗透测试 (IVPT) 研究，并在体内人血清 PK 评估期间保持严格的协调技术以控制应用时间、封闭、温度和湿度。目的是研究增加对实验参数的控制是否会导致常见局部制剂的受试者间变异性降低，从而导致可接受的 IVIVC 建立。使用基于反卷积的方法，所有四种防晒霜配方在整个 12 小时的研究持续时间内都实现了出色的点对点（A 级相关性）IVIVC，曲线下面积 (AUC) 和峰浓度 ( C max）估计。体内吸收数据的低可变性提供了一种概念验证协议设计，用于测试以可靠的方式在大表面积上应用的复杂半固体和液体局部制剂。这项工作还提供了扩展测试的机会，以测试温度和湿度变化条件对体内产品吸收的影响，并具有高精度。
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