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.

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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