Abstract/Details

Multiscale modeling of transdermal drug delivery


2006 2006

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Abstract (summary)

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin.

In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers.

Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly.

During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC).

A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a homogenization procedure is performed over a model unit cell of the heterogeneous SC, resulting in effective diffusion parameters. These effective parameters are the macroscopic diffusion coefficients for the homogeneous medium that is "equivalent" to the heterogeneous SC, and thus can be used in finite element simulations of the macroscopic diffusion process.

Indexing (details)


Subject
Materials science;
Mechanical engineering
Classification
0794: Materials science
0548: Mechanical engineering
Identifier / keyword
Applied sciences; Diffusion; Drug delivery; Multiscale; Transdermal
Title
Multiscale modeling of transdermal drug delivery
Author
Rim, Jee Eun
Number of pages
194
Publication year
2006
Degree date
2006
School code
0212
Source
DAI-B 67/03, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780542571275, 0542571277
Advisor
Pinsky, Peter M.
University/institution
Stanford University
University location
United States -- California
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3209014
ProQuest document ID
304978691
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304978691
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