A numerical model for transdermal drug delivery (TDD) has been developed by treating skin as a composite, dynamic, porous medium. Governing unsteady mass transport equations in porous medium was solved for different cases for up to a period of drug-patch application of 10 hrs. The effects of cell migration and anisotropic diffusive properties of stratum corneum (SC) on TDD are analyzed. Each of the above factors and their combination are found to significantly affect TDD. The cell migration in SC decreases the predicted amount of drug considerably. Their combined effect in TDD helped in identifying four distinct regimes of pharmacological as well as engineering importance within the domain.
Issue Section:
Research Papers
Keywords:
Bio-Heat and mass transfer
References
References
1.
Scheuplein
, R. J.
, 1967
, “Mechanism of Percutaneous Absorption
,” J. Invest. Dermatol.
, 48
(1
), pp. 79
–88
.2.
Hadgraft
, J.
, and Guy
, R. H.
, 1989
, Transdermal Drug Delivery: Developmental Issues and Research Initiatives
, Vol. 35
, Marcel Dekker
, New York
.3.
Waters
, C.
, 2013
, “The Development of the Rotigotine Transdermal Patch: A Historical Perspective
,” Neurol. Clin.
, 31
(Suppl. 3
), pp. S37
–S50
.4.
Wohlrab
, J.
, Kreft
, B.
, and Tamke
, B.
, 2011
, “Skin Tolerability of Transdermal Patches
,” Expert Opin. Drug Delivery
, 8
(7
), pp. 939
–948
.5.
Barry
, B.
, 2001
, “Novel Mechanisms and Devices to Enable Successful Transdermal Drug Delivery
,” Eur. J. Pharm. Sci.
, 14
(2
), pp. 101
–114
.6.
Kretsos
, K.
, Miller
, M. A.
, Zamora-Estrada
, G.
, and Kasting
, G. B.
, 2008
, “Partitioning, Diffusivity and Clearance of Skin Permeants in Mammalian Dermis
,” Int. J. Pharm.
, 346
(1–2
), pp. 64
–79
.7.
Khalil
, E.
, Kretsos
, K.
, and Kasting
, G.
, 2006
, “Glucose Partition Coefficient and Diffusivity in the Lower Skin Layers
,” Pharm. Res.
, 23
(6
), pp. 1227
–1234
.8.
Frederick Frasch
, H.
, 2002
, “A Random Walk Model of Skin Permeation
,” Risk Anal.
, 22
(2
), pp. 265
–276
.9.
Montagna
, W.
, 1974
, The Structure and Function of Skin 3E
, Academic Press
, New York
.10.
Heisig
, M.
, Lieckfeldt
, R.
, Wittum
, G.
, Mazurkevich
, G.
, and Lee
, G.
, 1996
, “Non Steady-State Descriptions of Drug Permeation Through Stratum Corneum. I. The Biphasic Brick-and-Mortar Model
,” Pharm. Res.
, 13
(3
), pp. 421
–426
.11.
Park
, J.-H.
, Choi
, S.-O.
, Seo
, S.
, Choy
, Y. B.
, and Prausnitz
, M. R.
, 2010
, “A Microneedle Roller for Transdermal Drug Delivery
,” Eur. J. Pharm. Biopharm.
, 76
(2
), pp. 282
–289
.12.
Petersen
, K. K.
, Rousing
, M. L.
, Jensen
, C.
, Arendt-Nielsen
, L.
, and Gazerani
, P.
, 2011
, “Effect of Local Controlled Heat on Transdermal Delivery of Nicotine
,” Int. J. Physiol., Pathophysiol. Pharmacol.
, 3
(3
), pp. 236
–242
.13.
Cross
, S. E.
, and Roberts
, M. S.
, 1995
, “Importance of Dermal Blood Supply and Epidermis on the Transdermal Iontophoretic Delivery of Monovalent Cations
,” J. Pharm. Sci.
, 84
(5
), pp. 584
–592
.14.
Hadgraft
, J.
, 1999
, “Passive Enhancement Strategies in Topical and Transdermal Drug Delivery
,” Int. J. Pharm.
, 184
(1
), pp. 1
–6
.15.
Kalia
, Y. N.
, and Guy
, R. H.
, 2001
, “Modeling Transdermal Drug Release
,” Adv. Drug Delivery Rev.
, 48
(2
), pp. 159
–172
.16.
Iordanskii
, A. L.
, Feldstein
, M. M.
, Markin
, V. S.
, Hadgraft
, J.
, and Plate
, N. A.
, 2000
, “Modeling of the Drug Delivery From a Hydrophilic Transdermal Therapeutic System Across Polymer Membrane
,” Eur. J. Pharm. Biopharm.
, 49
(3
), pp. 287
–293
.17.
Manitz
, R.
, Lucht
, W.
, Strehmel
, K.
, Weiner
, R.
, and Neubert
, R.
, 1998
, “On Mathematical Modeling of Dermal and Transdermal Drug Delivery
,” J. Pharm. Sci.
, 87
(7
), pp. 873
–879
.18.
Rim
, J. E.
, Pinsky
, P. M.
, and van Osdol
, W. W.
, 2009
, “Multiscale Modeling Framework of Transdermal Drug Delivery
,” Ann. Biomed. Eng.
, 37
(6
), pp. 1217
–1229
.19.
Lv
, Y.
, Liu
, J.
, Gao
, Y.
, and Xu
, B.
, 2006
, “Modeling of Transdermal Drug Delivery With a Microneedle Array
,” J. Micromech. Microeng.
, 16
(11
), pp. 2492
–2501
.20.
Mehdizadeh
, A.
, Toliate
, T.
, Rouini
, M. R.
, Abashzadeh
, S.
, and Dorkoosh
, F.
, 2004
, “Design and In Vitro Evaluation of New Drug-in-Adhesive Formulations of Fentanyl Transdermal Patches
,” Acta Pharm.
, 54
(4
), pp. 301
–317
.21.
Hadgraft
, J.
, and Guy
, R. H.
, 2010
, Transdermal Drug Delivery
, 2nd ed., Vol. 123
, Informa Healthcare
, London
.22.
Filer
, C.
, Allen
, G.
, Brown
, T.
, Fowles
, S.
, Hollis
, F.
, Mort
, E.
, Prince
, W.
, and Ramji
, J.
, 1994
, “Metabolic and Pharmacokinetic Studies Following Oral Administration of 14C-Famciclovir to Healthy Subjects
,” Xenobiotica
, 24
(4
), pp. 357
–368
.23.
Narasimhan
, A.
, 2013
, Essentials of Heat and Fluid Flow in Porous Media
, ANE Books
, New Delhi, India
.24.
Alberti
, I.
, Kalia
, Y. N.
, Naik
, A.
, Bonny
, J.-D.
, and Guy
, R. H.
, 2001
, “In Vivo Assessment of Enhanced Topical Delivery of Terbinafine to Human Stratum Corneum
,” J. Controlled Release
, 71
(3
), pp. 319
–327
.25.
Lowes
, M. A.
, Bowcock
, A. M.
, and Krueger
, J. G.
, 2007
, “Pathogenesis and Therapy of Psoriasis
,” Nature
, 445
(7130
), pp. 866
–873
.26.
Benson
, H. A.
, 2005
, “Transdermal Drug Delivery: Penetration Enhancement Techniques
,” Curr. Drug Delivery
, 2
(1
), pp. 23
–33
.27.
Kramer
, C.
, and Tawney
, M.
, 1998
, “A Fatal Overdose of Transdermally Administered Fentanyl
,” J. Am. Osteopath. Assoc.
, 98
(7
), pp. 385
–386
.28.
Tanner
, T.
, and Marks
, R.
, 2008
, “Delivering Drugs by the Transdermal Route: Review and Comment
,” Skin Res. Technol.
, 14
(3
), pp. 249
–260
.29.
Ale
, I.
, Lachapelle
, J.-M.
, and Maibach
, H.
, 2009
, “Skin Tolerability Associated With Transdermal Drug Delivery Systems: An Overview
,” Adv. Ther.
, 26
(10
), pp. 920
–935
.30.
Zhai
, H.
, and Maibach
, H. I.
, 2001
, “Skin Occlusion and Irritant and Allergic Contact Dermatitis: An Overview
,” Contact Dermatitis
, 44
(4
), pp. 201
–206
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