An evaluation of mathematical models for predicting skin permeability

Lian, Guoping; Chen, Longjian; Han, Lujia

doi:10.1002/jps.21074

Cited by 104 publications

(73 citation statements)

References 51 publications

(95 reference statements)

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“…Moreover, the SC is also known to exhibit selective permeability with respect to the type of diffusing molecules, meaning that the barrier nature of the skin imposes physicochemical limitations to the type of permeants that can traverse the skin, including hydrophilicity, size, hydrogen-bonding ability and so on (Akomeah et al, 2007;Lian et al, 2008;Potts and Guy, 1992). On the other hand, drugs can be encapsulated and located at different positions in the lipid vesicular system according to their lipophilicity.…”

Section: Introductionmentioning

confidence: 96%

Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application

Chen

Liu

Fahr

2011

International Journal of Pharmaceutics

152

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Section: Introductionmentioning

confidence: 96%

Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application

Chen

Liu

Fahr

2011

International Journal of Pharmaceutics

152

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“…[21][22][23] Most drugs used in TDDSs have MWs <500 Da, 24) and the P value through skin was reported previously to markedly decrease with an increase in MW >500 Da. Furthermore, the P values of drugs increased with increasing log K o/w .…”

mentioning

confidence: 99%

Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds

Uchida

Yakumaru

Nishioka

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL 2 ), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL 2 , and log KL values between the silicone membrane and human skin. DL 2 values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL 2 and KL, were similar. For lipophilic compounds, such as nbutyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log K o/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over-or underestimated.Key words silicone membrane; skin; membrane permeation; alternative membrane Skin forms an interface between the body and environment and functions as a firm barrier against undesirable elements. Many skin permeation studies of therapeutic drugs have been conducted to develop transdermal drug delivery systems (TDDSs) for the purpose of preventing the hepatic first-pass effect, which is observed for some oral dosage forms, and for controlling release over long periods of time.1-3) For the development and evaluation of TDDSs, in vitro skin permeation tests using excised human skin have been performed in the European Union (EU) and United States; however, in Japan, it is difficult to obtain human skin, so permeation studies using human skin are not performed as frequently. Therefore, animal skins, particularly those of hairless rat, mouse, and guinea pig, have been used for the evaluation of percutaneous absorption. Recently, however, sales of cosmetics in the EU, 4) for which animal experiments were performed during their development have been prohibited out of concern for animal welfare, and alternative membranes are now required to determine percutaneous absorption. In addition, permeation studies using animal or human skin are associated with several difficulties and limitations for assessing the effects of formulations components, because of the complex nature of this biological tissue and inter- and intra-individuality of skin.Artificial model membranes offer a simple and ...

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“…[91][92][93][94][95] Lipophilicity and molecular weight are among the most important factors determining the ability of compounds to permeate the skin. 96 In addition, the density, viscosity, and lipophilicity of vehicles have a huge impact on permeation rates, which is why much research in pharmacokinetics is focused on finding better vehicles for drug delivery. Most models use the quantity of test compound that passively diffuses through the skin of a donor as the measure of penetration (i.e., most models predict the permeation rate constant [Kp]).…”

Section: In Silico Methodsmentioning

confidence: 99%

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

DumontCoralie

PrietoPilar

AsturiolDavid

et al. 2015

Applied In Vitro Toxicology

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The exposure of the skin to consumer products, drugs, and environmental chemicals can result in their penetrating the skin barrier and entering systemic circulation, potentially resulting in adverse effects in the skin and other organs. The assessment of dermal penetration and bioavailability (including penetration, metabolism, and entry into the systemic circulation) is therefore an important consideration in the risk assessment of chemicals. The skin is a heterogeneous organ with a multilayer structure. Based on its architecture and physiology, substances can penetrate through three major ways but can also be blocked in the different skin layers and in the skin appendages, which act as reservoir. In addition to that, as the skin is a metabolically competent organ, substances can undergo metabolism. After a brief description of the skin architecture, this review will focus on the skin penetration mechanisms and skin metabolic capacities. The skin absorption has traditionally been tested in vivo on animals. However, with the new legislation (i.e., Registration, Evaluation, Authorisation, and Restriction of Chemicals Regulation or Cosmetics Regulation), alternatives to animal testing have to be implemented. In a second part, this review will provide a description of the main in vitro and in silico or computational models available to study skin absorption and skin metabolism (i.e., ex vivo skin models, artificial membrane barriers, primary cells and cell lines, Quantitative Structure-Activity Relationship [QSAR], simulators for the prediction of skin metabolism).

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An evaluation of mathematical models for predicting skin permeability

Cited by 104 publications

References 51 publications

Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application

Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application

Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

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