Sinkó Bálint, Bárdos Vivien, Vesztergombi Dániel, Kádár Szabina, Malcsiner Petra, Moustie Anne, Jouy Chantal, Takács-Novák Krisztina, Grégoire Sebastien
Department of Pharmaceutical Chemistry, Semmelweis University, H-1092 Budapest, Hungary.
Pion Inc., Billerica, MA 01821, USA.
Pharmaceutics. 2021 Oct 21;13(11):1758. doi: 10.3390/pharmaceutics13111758.
Absorption through the skin of topically applied chemicals is relevant for both formulation development and safety assessment, especially in the early stages of development. However, the supply of human skin is limited, and the traditional in vitro methods are of low throughput. As an alternative, an artificial membrane-based Skin Parallel Artificial Membrane Permeability Assay (Skin-PAMPA) has been developed to mimic the permeability through the stratum corneum. In this study, this assay was used to measure the permeability of a model compound, 4-phenylethyl-resorcinol (PER), dissolved in 13 different solvents that are commonly used in cosmetic formulation development. The study was performed at concentrations close to the saturated solution of PER in each solvent to investigate the maximum thermodynamic potential of the solvents. The permeability of PER in selected solvents was also measured on ex vivo pig skin for comparison. Pig ear skin is an accepted alternative model of human skin. The permeability coefficient, which is independent of the concentration of the applied solution, showed a good correlation ( = 0.844) between the Skin-PAMPA and the pig skin permeation data. Our results support the use of the Skin-PAMPA to screen the suitability of different solvents for non-polar compounds at an early stage of formulation development.
局部应用化学品经皮肤吸收对于制剂开发和安全性评估都很重要，尤其是在开发的早期阶段。然而，人体皮肤的供应有限，传统的体外方法通量较低。作为一种替代方法，已开发出一种基于人工膜的皮肤平行人工膜渗透试验（Skin-PAMPA）来模拟通过角质层的渗透性。在本研究中，该试验用于测量一种模型化合物4-苯乙基间苯二酚（PER）在13种常用于化妆品制剂开发的不同溶剂中的渗透性。该研究在接近PER在每种溶剂中的饱和溶液浓度下进行，以研究溶剂的最大热力学潜力。还在离体猪皮上测量了PER在选定溶剂中的渗透性以作比较。猪耳皮肤是一种公认的人体皮肤替代模型。与所施加溶液浓度无关的渗透系数在Skin-PAMPA和猪皮渗透数据之间显示出良好的相关性（ = 0.844）。我们的结果支持在制剂开发的早期阶段使用Skin-PAMPA来筛选不同溶剂对非极性化合物的适用性。
