Matharoo Namrata S, Garimella Harsha T, Truong Thu M, Badeti Saiaditya, Cui Joyce X, Talluri Sesha Rajeswari, Virani Amitkumar, Rao Babar K, Michniak-Kohn Bozena
Center for Dermal Research, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA.
Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd, Piscataway, NJ 08854, USA.
Pharmaceutics. 2025 Aug 25;17(9):1108. doi: 10.3390/pharmaceutics17091108.
Adapalene is a synthetic retinoid used as a treatment for acne vulgaris. In this study, we attempted to evaluate the dermal pharmacokinetics of adapalene utilizing experimental and in silico tools. We utilized three over the counter (OTC) adapalene gels to evaluate local dermal pharmacokinetics. A data-driven, robust, mechanistic dermal physiologically based pharmacokinetic (PBPK) model was developed by integrating the physicochemical properties of adapalene, the formulation attributes of the gels, and the biophysical aspects of dermal absorption. The dermal PBPK model was validated against experimental data using in vitro release studies and in vitro permeation studies with human cadaver skin. A clinical study was performed to evaluate the effects of adapalene from the three gel formulations. The impact of adapalene delivery from three gels on the stratum corneum (SC) thickness, pilosebaceous unit area, keratinocyte number, and epidermal thickness was captured using a non-invasive technique, line-field confocal optical coherence tomography (LC-OCT). These responses were evaluated using an Emax model. The dermal PBPK model has successfully predicted adapalene penetration profiles across different gel formulations. The model accuracy, in predicting drug release and permeation characteristics, was confirmed using the experimental data. Clinical evaluation revealed formulation-dependent differences in adapalene's effects on measured skin parameters, with distinct pharmacodynamic profiles observed for each gel formulation. The overall study gave us a detailed insight into potential effects of formulation on the dermal pharmacokinetics and pharmacodynamics of adapalene using three marketed gels.
阿达帕林是一种用于治疗寻常痤疮的合成维甲酸。在本研究中，我们试图利用实验和计算机模拟工具评估阿达帕林的皮肤药代动力学。我们使用了三种非处方（OTC）阿达帕林凝胶来评估局部皮肤药代动力学。通过整合阿达帕林的物理化学性质、凝胶的制剂属性以及皮肤吸收的生物物理方面，建立了一个数据驱动、稳健的基于皮肤生理的药代动力学（PBPK）模型。使用体外释放研究和人尸体皮肤的体外渗透研究，根据实验数据对皮肤PBPK模型进行了验证。进行了一项临床研究，以评估三种凝胶制剂中阿达帕林的效果。使用非侵入性技术——线场共聚焦光学相干断层扫描（LC-OCT），捕捉了三种凝胶中阿达帕林给药对角质层（SC）厚度、毛囊皮脂腺单位面积、角质形成细胞数量和表皮厚度的影响。使用Emax模型对这些反应进行了评估。皮肤PBPK模型成功预测了阿达帕林在不同凝胶制剂中的渗透情况。使用实验数据证实了该模型在预测药物释放和渗透特性方面的准确性。临床评估显示，阿达帕林对所测皮肤参数的影响存在制剂依赖性差异，每种凝胶制剂都观察到了不同的药效学特征。总体研究让我们深入了解了使用三种市售凝胶时制剂对阿达帕林皮肤药代动力学和药效学的潜在影响。
