A transdermal/topical absorption classification system for the characterization of the systemic or local delivery of drugs is the theoretical basis for the design and evaluation of transdermal/topical formulations. A classification system was established on the basis of the in vitro and in vivo skin permeation/retention behaviors of 12 model drugs. Drug skin penetration/retention exhibited a significant correlation with physicochemical parameters (log K_O/W, molecular weight, polar surface area, and polarizability). Four representative model drugs were selected to clarify the molecular mechanisms of drug skin permeation/retention behaviors. The excellent lipid-disrupting effect and enhanced partitioning exhibited by propranolol (high permeation–high retention) and zolmitriptan (high permeation-low retention) via the formation of moderate H-bonds with skin lipids were proven by ATR–FTIR (Δν_asCH2 > 2 cm⁻¹), Raman spectra (ΔLPP, SPP > 0.2 nm), and X-ray scattering (lipid crystallization) and were supported by ¹³C NMR results. The low lipid miscibility of zolmitriptan (ΔH_{zolmitriptan-lipid} = 126.92 J/g) caused the low skin retention of this drug. High polarizabiltiy (α = 38.5 × 10⁻²⁴ cm³) and low H-bond forming capability (E_H-bond = 0 kcal/mol) restricted terbinafine (low permeation–high retention) in terms of partitioning (k_D-SC = 0.09). Diclofenac (low permeation–low retention) stabilized skin lipids through the formation of strong H-bonds and exhibited excessive drug–lipid miscibility (ΔH_{diclofenac-skin} = −128.73 J/g), thus restricting its skin absorption. This classification system reflects the most essential drug skin absorption characteristics and provides a theoretical basis for the design of transdermal/topical formulations.

用于表征药物全身或局部递送的透皮/局部吸收分类系统是设计和评估透皮/局部制剂的理论基础。的分类系统建立的基础上在体外和体内皮肤渗透/保留的12种模型药物的行为。药物皮肤渗透/保留表现出与理化参数（log K _O/W、分子量、极性表面积和极化率）。选择了四种具有代表性的模型药物来阐明药物皮肤渗透/滞留行为的分子机制。通过适度氢键与皮肤脂质的形成优异的脂质破坏作用，并通过普萘洛尔表现出增强的分区（高渗透高保持率）和佐米曲普坦（高渗透低保留）通过ATR-FTIR（Δ证明ν _asCH2  > 2 cm ^-1 )、拉曼光谱（ΔLPP，SPP > 0.2 nm）和 X 射线散射（脂质结晶）并得到¹³ C NMR 结果的支持。佐米曲坦的低脂溶性（ΔH _{zolmitriptan-lipid} = 126.92 J/g) 导致该药物的皮肤滞留率低。高极化率 ( α  = 38.5 × 10 ^-24 cm ³ ) 和低氢键形成能力 ( E _{H 键} = 0 kcal/mol) 限制了特比萘芬（低渗透 - 高保留）在分配方面（k _D-SC  = 0.09）。双氯芬酸（低渗透-低保留）通过形成强氢键稳定皮肤脂质，并表现出过度的药物-脂质混溶性（ΔH_{双氯芬酸-皮肤} = -128.73 J/g)，从而限制其皮肤吸收。该分类体系反映了最基本的药物皮肤吸收特性，为透皮/外用制剂的设计提供了理论依据。