Modeling transdermal permeation. Part 2. Predicting the dermatopharmacokinetics of percutaneous solute

Abstract

The prediction of percutaneous absorption and bioavailability in vivo, using the recently reported "bricks-and-mortar" model is discussed. Two sets of in vivo data have been simulated: the tape-striping data of 4-cyanophenol and Raman spectrometry data of transretinol. The predicted transdermal permeation using theoretically derived properties agreed well with the experimental data. The prediction shows that about 2/3 of the 4-cynophenol in the SC partitioned into the corneocytes, indicating diffusion of moderately hydrophobic solutes across the corneocytes is also important. Only for highly hydrophobic solute like transretinol, diffusion across the corneocytes is negligibly small. The study demonstrates that with the mechanism-based computer model, many dermatopharmacokinetic parameters can be derived, providing much insight into how vehicle formulation and topical administration affects the absorption and distribution of solute in the SC, as well as its bioavailability in epidermis/dermis. © 2010 American Institute of Chemical Engineers (AIChE)

Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration

“…The partitions included in Table 1 correspond to their Model 2, fully hydrated SC. In Chen et al [52–55], for K ow ≥ 10, K cor is computed with Eq. (2) but for K ow < 10, K cor is computed as function of K lip , as shown in Table 1.…”

“…(3) the expected range of values of D cor is 1 × 10 −6 to 1 × 10 −5 cm 2 /s for a wide range of molecular volumes. On the contrary, the corneocyte diffusivity in Chen et al [52–55] ranges from 1.4 × 10 −12 to 6.6 × 10 −11 cm 2 /s and includes hindrance parameters adjusted to match permeability data.…”

“…Wang et al [4,51] introduced anisotropy in the lipid layers mathematically represented with a lateral diffusivity and a mass transfer coefficient for transbilayer hopping, with the lipid phase being the main diffusion barrier. Chen et al’s model (2008) [52–55] included an isotropic lipid phase with the corneocyte being the main barrier to diffusion. In summary, of the most recent models, Wang et al [4,51] and Johnson et al [48] models locate the main barrier in the lipid phase, while Naegel-Hansen [35,47] and Chen et al [52–55] models consider the corneocyte phase as the leading barrier.…”

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…This represents significant progress of simple permeability models. It has been demonstrated that such mechanistic models are fully capable of predicting absorbed dose and subcellular distribution of chemicals from formulated products under in vivo exposure conditions (Lian et al, 2010).…”

Measuring the Penetration of a Skin Sensitizer and Its Delivery Vehicles Simultaneously with Confocal Raman Spectroscopy

“…The in vitro data (or indeed in vivo data [15] ) generated by confocal Raman spectroscopy could be used to refine such assumptions and to investigate behaviour in formulations more akin to those found in consumer personal care products. Additionally, such data can be used in mathematical models predictive of skin absorption, either for refining the input data for mechanistic physiochemically based models and/or evaluating their predictive performance [49] .…”