Lehman Paul A
QPS, LLC, Delaware Technology Park, Newark,Delaware 19811.
J Pharm Sci. 2014 Dec;103(12):4048-4057. doi: 10.1002/jps.24189. Epub 2014 Oct 16.
Historically, percutaneous absorption permeation parameters have been derived from in vitro infinite dose studies, yet there is uncertainty in their accuracy if the applied vehicle saturates or damages the stratum corneum, or when the permeation parameters are inappropriately derived from cumulative absorption data. An approach is provided for determining penetration parameters from in vitro finite dose data. Key variables, and equations for their derivation, are identified from the literature and provide permeation parameters that use only Tmax , AUC, and AUMC from finite dose data. The equations are tested with computer-generated model data and to actual study data. Derived permeation parameters obtained from the computer model data match those used in generating the simulated finite dose data. Parameters obtained from actual study data reasonably and acceptably model the penetration profile kinetics of the study data. From in vitro finite dose absorption data, three parameters can be obtained: the diffusion transit time (td ), which characterizes the diffusion coefficient, the partition volume (Vm P), which characterizes the partition coefficient, and the permeation coefficient (Kp ). These parameters can be obtained from finite dose data without having to know the length of the diffusion pathway through the membrane.
从历史上看，经皮吸收渗透参数是通过体外无限剂量研究得出的，然而，如果所应用的载体使角质层饱和或受损，或者当渗透参数不适当地从累积吸收数据中得出时，其准确性存在不确定性。本文提供了一种从体外有限剂量数据确定渗透参数的方法。从文献中确定了关键变量及其推导方程，并提供了仅使用有限剂量数据中的Tmax、AUC和AUMC的渗透参数。这些方程用计算机生成的模型数据和实际研究数据进行了测试。从计算机模型数据中获得的推导渗透参数与生成模拟有限剂量数据时使用的参数相匹配。从实际研究数据中获得的参数合理且可接受地模拟了研究数据的渗透曲线动力学。从体外有限剂量吸收数据中，可以获得三个参数：表征扩散系数的扩散传输时间（td）、表征分配系数的分配体积（Vm P）和渗透系数（Kp）。这些参数可以从有限剂量数据中获得，而无需知道通过膜的扩散途径的长度。
