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Steady‐State Flux and Lag Time in the Stratum Corneum Lipid Pathway: Results from Finite Element Models
Finite element model (FEM) solutions of the diffusion through two‐dimensional representations of the stratum corneum (SC) lipid pathway are presented. Both simplified, regular “brick and mortar” models and a more complex, irregular model are analyzed. It is assumed that diffusion occurs only within...
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Published in: | Journal of pharmaceutical sciences 2003-11, Vol.92 (11), p.2196-2207 |
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description | Finite element model (FEM) solutions of the diffusion through two‐dimensional representations of the stratum corneum (SC) lipid pathway are presented. Both simplified, regular “brick and mortar” models and a more complex, irregular model are analyzed. It is assumed that diffusion occurs only within the SC lipids and the lipids are isotropic. The steady‐state flux and lag time are solved and compared with the corresponding values for a homogeneous membrane of the same thickness consisting of lipid material. Results confirm that the heterogeneous SC model behaves like a homogeneous membrane, meaning that FEM diffusion simulations are well approximated by an appropriate solution of the diffusion equation for a homogeneous membrane. Additionally, both steady‐state flux and lag time (relative to these values in a homogeneous membrane) can be predicted from algebraic equations based on simple dimensionless descriptors of SC geometry. However, values for diffusivity derived from homogeneous membrane approximations to the FEM solutions (effective diffusivity, D*) are not equal to the intrinsic diffusivity of the chemical in lipid. Furthermore, the pathlength derived from homogeneous membrane approximations to FEM solutions (effective pathlength, l*) is not equal to the lipid pathlength and is not dependent on SC tortuosity. Whereas l* is not a function of corneocyte overlap, D* is. These model results suggest that diffusion properties of the SC lipid pathway can be correlated to SC geometry, but intrinsic diffusion coefficients and SC tortuosity cannot be derived from common diffusion cell experiments. Use of the model equations to predict permeability and lag time of lipophilic solutes is described. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2196–2207, 2003 |
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Both simplified, regular “brick and mortar” models and a more complex, irregular model are analyzed. It is assumed that diffusion occurs only within the SC lipids and the lipids are isotropic. The steady‐state flux and lag time are solved and compared with the corresponding values for a homogeneous membrane of the same thickness consisting of lipid material. Results confirm that the heterogeneous SC model behaves like a homogeneous membrane, meaning that FEM diffusion simulations are well approximated by an appropriate solution of the diffusion equation for a homogeneous membrane. Additionally, both steady‐state flux and lag time (relative to these values in a homogeneous membrane) can be predicted from algebraic equations based on simple dimensionless descriptors of SC geometry. However, values for diffusivity derived from homogeneous membrane approximations to the FEM solutions (effective diffusivity, D*) are not equal to the intrinsic diffusivity of the chemical in lipid. Furthermore, the pathlength derived from homogeneous membrane approximations to FEM solutions (effective pathlength, l*) is not equal to the lipid pathlength and is not dependent on SC tortuosity. Whereas l* is not a function of corneocyte overlap, D* is. These model results suggest that diffusion properties of the SC lipid pathway can be correlated to SC geometry, but intrinsic diffusion coefficients and SC tortuosity cannot be derived from common diffusion cell experiments. Use of the model equations to predict permeability and lag time of lipophilic solutes is described. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2196–2207, 2003</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.10466</identifier><identifier>PMID: 14603505</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Hoboken: Elsevier Inc</publisher><subject>Algorithms ; Animals ; Biological and medical sciences ; Cell physiology ; Diffusion ; Finite Element Analysis ; Fundamental and applied biological sciences. Psychology ; General pharmacology ; In Vitro Techniques ; lag time ; Lipid Metabolism ; mathematical model ; Medical sciences ; Membrane and intracellular transports ; Mice ; Models, Statistical ; Molecular and cellular biology ; percutaneous ; permeability ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. 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Both simplified, regular “brick and mortar” models and a more complex, irregular model are analyzed. It is assumed that diffusion occurs only within the SC lipids and the lipids are isotropic. The steady‐state flux and lag time are solved and compared with the corresponding values for a homogeneous membrane of the same thickness consisting of lipid material. Results confirm that the heterogeneous SC model behaves like a homogeneous membrane, meaning that FEM diffusion simulations are well approximated by an appropriate solution of the diffusion equation for a homogeneous membrane. Additionally, both steady‐state flux and lag time (relative to these values in a homogeneous membrane) can be predicted from algebraic equations based on simple dimensionless descriptors of SC geometry. However, values for diffusivity derived from homogeneous membrane approximations to the FEM solutions (effective diffusivity, D*) are not equal to the intrinsic diffusivity of the chemical in lipid. Furthermore, the pathlength derived from homogeneous membrane approximations to FEM solutions (effective pathlength, l*) is not equal to the lipid pathlength and is not dependent on SC tortuosity. Whereas l* is not a function of corneocyte overlap, D* is. These model results suggest that diffusion properties of the SC lipid pathway can be correlated to SC geometry, but intrinsic diffusion coefficients and SC tortuosity cannot be derived from common diffusion cell experiments. Use of the model equations to predict permeability and lag time of lipophilic solutes is described. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2196–2207, 2003</description><subject>Algorithms</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell physiology</subject><subject>Diffusion</subject><subject>Finite Element Analysis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General pharmacology</subject><subject>In Vitro Techniques</subject><subject>lag time</subject><subject>Lipid Metabolism</subject><subject>mathematical model</subject><subject>Medical sciences</subject><subject>Membrane and intracellular transports</subject><subject>Mice</subject><subject>Models, Statistical</subject><subject>Molecular and cellular biology</subject><subject>percutaneous</subject><subject>permeability</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Regression Analysis</subject><subject>skin</subject><subject>Skin - metabolism</subject><subject>transdermal</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNp1kM1uEzEQxy0EoqFw4AWQLyBxWDq21w7LDUUNHwqiIuVsTexZ6mo_UttLyY1H6DP2STAkqBeQLI2l-c1_Rj_Gngp4JQDkyeU2lU9tzD02E1pCZUDM77NZ6clK6bo5Yo9SugQAA1o_ZEeiNqA06BkL60zod7c_b9YZM_FlN_3gOHi-wm_8PPTEw8DzBfF1jpinni_GOFCpq7ANnp9hvrjG3Rv-hdLU5cTbOPZ8GYZQsk476mnI_NPoqUuP2YMWu0RPDvWYfV2eni_eV6vP7z4s3q4qpxptqloaVK8lmVajwaYl7ZUiX95GkJuDqZsavNoIZ5SkuccGhIDWeQOtQuPVMXuxz93G8WqilG0fkqOuw4HGKdm5UEpKkAV8uQddHFOK1NptDD3GnRVgf3u1xav947Wwzw6h06Ynf0ceRBbg-QHA5LBrIw4upDtOS9UIqQp3sueuQ0e7_2-0H8_Wf1er_URxSN8DRZtcoMGRD5Fctn4M_zj4F8aMoTU</recordid><startdate>200311</startdate><enddate>200311</enddate><creator>Frederick Frasch, H.</creator><creator>Barbero, Ana M.</creator><general>Elsevier Inc</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>American Pharmaceutical Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200311</creationdate><title>Steady‐State Flux and Lag Time in the Stratum Corneum Lipid Pathway: Results from Finite Element Models</title><author>Frederick Frasch, H. ; Barbero, Ana M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3956-426a382e6f5a6a9fe5d33ed3edb1ec7064940d3b1c632e7da90110fcd60f3a6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Algorithms</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell physiology</topic><topic>Diffusion</topic><topic>Finite Element Analysis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General pharmacology</topic><topic>In Vitro Techniques</topic><topic>lag time</topic><topic>Lipid Metabolism</topic><topic>mathematical model</topic><topic>Medical sciences</topic><topic>Membrane and intracellular transports</topic><topic>Mice</topic><topic>Models, Statistical</topic><topic>Molecular and cellular biology</topic><topic>percutaneous</topic><topic>permeability</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Regression Analysis</topic><topic>skin</topic><topic>Skin - metabolism</topic><topic>transdermal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frederick Frasch, H.</creatorcontrib><creatorcontrib>Barbero, Ana M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frederick Frasch, H.</au><au>Barbero, Ana M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Steady‐State Flux and Lag Time in the Stratum Corneum Lipid Pathway: Results from Finite Element Models</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J Pharm Sci</addtitle><date>2003-11</date><risdate>2003</risdate><volume>92</volume><issue>11</issue><spage>2196</spage><epage>2207</epage><pages>2196-2207</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>Finite element model (FEM) solutions of the diffusion through two‐dimensional representations of the stratum corneum (SC) lipid pathway are presented. Both simplified, regular “brick and mortar” models and a more complex, irregular model are analyzed. It is assumed that diffusion occurs only within the SC lipids and the lipids are isotropic. The steady‐state flux and lag time are solved and compared with the corresponding values for a homogeneous membrane of the same thickness consisting of lipid material. Results confirm that the heterogeneous SC model behaves like a homogeneous membrane, meaning that FEM diffusion simulations are well approximated by an appropriate solution of the diffusion equation for a homogeneous membrane. Additionally, both steady‐state flux and lag time (relative to these values in a homogeneous membrane) can be predicted from algebraic equations based on simple dimensionless descriptors of SC geometry. However, values for diffusivity derived from homogeneous membrane approximations to the FEM solutions (effective diffusivity, D*) are not equal to the intrinsic diffusivity of the chemical in lipid. Furthermore, the pathlength derived from homogeneous membrane approximations to FEM solutions (effective pathlength, l*) is not equal to the lipid pathlength and is not dependent on SC tortuosity. Whereas l* is not a function of corneocyte overlap, D* is. These model results suggest that diffusion properties of the SC lipid pathway can be correlated to SC geometry, but intrinsic diffusion coefficients and SC tortuosity cannot be derived from common diffusion cell experiments. Use of the model equations to predict permeability and lag time of lipophilic solutes is described. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2196–2207, 2003</abstract><cop>Hoboken</cop><pub>Elsevier Inc</pub><pmid>14603505</pmid><doi>10.1002/jps.10466</doi><tpages>12</tpages></addata></record> |
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subjects | Algorithms Animals Biological and medical sciences Cell physiology Diffusion Finite Element Analysis Fundamental and applied biological sciences. Psychology General pharmacology In Vitro Techniques lag time Lipid Metabolism mathematical model Medical sciences Membrane and intracellular transports Mice Models, Statistical Molecular and cellular biology percutaneous permeability Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Regression Analysis skin Skin - metabolism transdermal |
title | Steady‐State Flux and Lag Time in the Stratum Corneum Lipid Pathway: Results from Finite Element Models |
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