Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 167, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2021.105924
Keywords
Transdermal; Dermal; Absorption; Integrated; Model; Computational; PBPK; Pharmacology; Skin; Patch
Categories
Funding
- National Institutes of Health/U
- S. Food and Administration under the Small Business Innovation Research (SBIR) [1R43FD005345-01A1, 2R44FD005345-02]
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Transdermal drug delivery systems offer advantages such as controlled release and reduced dosing frequency. An integrated biophysical model combines healthy skin and whole-body physiology to simulate compound permeation and absorption. This model can provide insights for optimizing delivery systems and understanding the absorption of transdermal formulations.
The delivery of therapeutic drugs through the skin is a promising alternative to oral or parenteral delivery routes because dermal drug delivery systems (D(3)Ss) offer unique advantages, such as controlled drug release over sustained periods and a significant reduction in first-pass effects, thus reducing the required dosing frequency and the level of patient noncompliance. Furthermore, D(3)Ss find applications in multiple therapeutic areas, including drug repurposing. This article presents an integrated biophysical model of dermal absorption for simulating the permeation and absorption of compounds delivered transdermally. The biophysical model is physiologically/biologically inspired and combines a holistic model of healthy skin with whole-body physiology based pharmacokinetics through the dermis microcirculation. The model also includes the effects of chemical penetration enhancers and hair follicles on transdermal transport. The model-predicted permeation and pharmacokinetics of select compounds were validated using in vivo data reported in the literature. We conjecture that the integrated model can be used to gather insights into the permeation and systemic absorption of transdermal formulations (including cosmetic products) released from novel depots and to optimize delivery systems. Furthermore, the model can be extended to diseased skin with parametrization and structural adjustments specific to skin diseases.
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