ORIGINAL PAPER
Drug Diffusion Transport Through Human Skin
 
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1
University of Zielona Góra, Faculty of Mechanical Engineering, ul. Szafrana 4, 65-516, Zielona Góra, Poland
 
2
University Hospital of Zielona Góra, Oncology Department ul. Zyty 26, 65-046 , Zielona Góra, Poland
 
 
Online publication date: 2018-11-21
 
 
Publication date: 2018-11-01
 
 
International Journal of Applied Mechanics and Engineering 2018;23(4):977-988
 
KEYWORDS
ABSTRACT
The stratum corneum (SC) forms the outermost layer of the human skin and is essentially a multilamellar lipid milieu punctuated by protein-filled corneocytes that augment membrane integrity and significantly increase membrane tortuosity. The lipophilic character of the SC, coupled with its intrinsic tortuosity, ensure that it almost always provides the principal barrier to the entry of drug molecules into the organism. Drugs can be administered either as suspensions or as solutions and the formulation can range in complexity from a gel or and ointment to a multilayer transdermal path. In this paper, we discuss theoretical principles used to describe transdermal release and we show that relatively simple membrane transport models based on the appropriate solution to the Fick’s second law of diffusion can be used to explain drug release kinetics into such a complex biological membrane as the human skin. To apply the Fick’s law we introduced into our considerations a brick-and-mortar model with two factors of tortuosity. Assuming that the mortar thickness is variable we also introduced the hindrance factor allowing us to model this variability. Having the modified Fick’s equation we presented its general solution and two special cases of this solution frequently applicable in permeation experiments. It seems that the solutions presented herein better approximate the real conditions of drug delivery then these well known.
 
REFERENCES (35)
1.
Kalia Y.N. and Guy R.H. (2001): Modeling transdermal drug release. – Adv. Drug Delivery Rev., vol.48, pp.159-172.
 
2.
Carreras N., Alonso C., Marti M. and Lis M.J. (2015): Mass transport model through the skin by microencapsulation system. – J. Microencapsulation, vol.32, No.4, pp.358-363.
 
3.
Cal K. (2009): Across skin barrier; known methods, new performances. – In: Frontiers in Drug Design and Discovery, vol.4 (Caldwell G.W., ur-Rahman A., Yan Z., Choudhary M.J., Eds), pp.162-188.
 
4.
Cal K. and Stefanowska J. (2010): Methods for skin permeation enhancement of drug substances. – Technology of drug form (in Polish: Technologia postaci leku), vol.66, No.7, pp.514-520.
 
5.
Glogau R.G. (2007): Topically applied botulinum toxin type A for the treatment of primary axillary hyperhidrosis: results of randomized, blinded, vehicle-controlled study. – Dermatol. Surg., vol.33, pp.76-80.
 
6.
Prausnitz M.R. and Langer R. (2008): Transdermal drug delivery. – Nat. Biotechnol., vol.26, No.11, pp.1261-1268.
 
7.
Ahluwalic A. (1998): Topical glucocorticosteroids and the skin-mechanism of action. – Med. Inflam., vol.7, pp.183-193.
 
8.
Higuchi T. (1960): Physical chemical analysis of percutaneous absorption process from creams and ointments. – J. Soc. Cosmet. Chem., vol.11, pp.85-97.
 
9.
Higuchi T. (1961): Rate of release of medicaments from ointment basis containing drugs in suspension. – J. Pharm. Sci., vol.50, pp.874-875.
 
10.
Michaels A.S., Chandraskeran S.K. and Shaw J.E. (1975): Drug permeation through human skin: theory and in vitro experimental measurement. – Amer. Inst. Chem. Eng., vol.21, No.5, pp.985-996.
 
11.
Bunge A.L. (1998): Release rate from topical formulations containing drugs in suspension. – J. Control. Rel., vol.52, No.1, pp.141-148.
 
12.
Hadgraft J. (1979): Calculations of drug release rates from controlled release devices. The slab. – Int. J. Pharmaceutics, vol.2, pp.177-194.
 
13.
Guy R.H. and Hadgraft J. (1980): A theoretical description relating skin penetration to the thickness of the applied medicament. – Int. J. Pharmaceutics, vol.6, pp.321-332.
 
14.
Johnson M.E., Blankshtein D. and Langer R. (1997): Evaluation of solute permeation through the stratum corneum: lateral bilayer diffusion as the primary mechanism. – J. Pharm. Sci., vol.86, No.10, pp.1162-1172.
 
15.
Ouriemchi E.M. and Vernaud J.M. (2000): Processes of drug transfer with three different polymeric systems with transdermal drug delivery. – Comp. Theor. Polymer Sci., vol.10, pp.391-401.
 
16.
Coceani N., Colombo I. and Grassi M. (2003): Acyclovir permeation through rat skin: mathematical modelling and vitro experiments. – Int. J. Pharmaceutics, vol.254, pp.197-210.
 
17.
Yamashita F. and Hashida M. (2003): Mechanistic and empirical modeling of skin permeation of drugs. – Adv. Drug Delivery Rev., vol.55, pp.1185-1199.
 
18.
He N., Waner K.S., Higuchi W.I. and Li K. (2005): Model analysis of flux enhancement across hairless mouse skin induced by chemical permeation enhancers. – Int. J. Pharmaceutics, vol.297, pp.9-21.
 
19.
Herkenne C., Naik A., Kalia Y.N., Hadgraft J. and Guy R. (2008): Effect of propylene glycol on ibuprofen absorption into human skin in vivo. – J. Pharm. Sci., vol.97, No.1, pp.185-197.
 
20.
Grassi M. (2008): Membranes in drug delivery. – In: Handbook of Membrane Separations: Chemical, Pharmaceutical, Food and Biotechnological Applications (Pabby A.K., Rizvi S.S.H. and Sastre A.M., Eds), CRC Press, New York, pp.427-464.
 
21.
Walicka A. (2017): Rheology of Fluids in Mechanical Engineering. – Zielona Góra: University Press.
 
22.
Walicka A., Walicki E., Jurczak P. and Falicki J. (2018): Effect of hindrance factors on a squeeze film of a porous bearing with a DeHaven fluid. – Submited to: Machine Dynamics Research.
 
23.
Milington P.F. and Wilkinson R. (1983): Skin. – Cambridge University Press.
 
24.
Bouwstra J.A., Honeywell-Nguyen P.L., Gooris G.S. and Ponec M. (2003): Structure of the skin barrier and its modulation by vesticular formulations. – Progress in Lipid Research, vol.42, No.1, pp.1-36.
 
25.
Madison K.C. (2003): Barrier function of the skin:,, la raison d’Être” of the epidermis. – Journal of Investigative Dermatology, vol.121, No.2, pp.231-241.
 
26.
Kushner J., Deen W.: Blankshtein D. and Langer R. (2007): First-principles, structure-based transdermal transport model to evaluate lipid partition and diffusion coefficients of hydrophobic permeants soley from stratum corneum permeation experiments. – J. Pharm. Sci., vol.96, No.12, pp.3236-3251.
 
27.
Walicka A. (2018a): Simulation of the flow through porous layer composed of converging-diverging capillary fissures and tubes. – Int. J. Appl. Mech. Eng., vol.23, No.1, pp.161-185.
 
28.
Walicka A. (2018b): Flows of Newtonian and power-law fluids in symmetrically corrugated fissures and tubes. – Int. J. Appl. Mech. Eng., vol.23, No.1, pp.187-215.
 
29.
Picioreanu C., van Loosdrecht M.C.M. and Heijnen J.J. (2001): Two-dimensional model of biofilm detachment caused by internal stress from liquid flow. – Biotech. Bioeng., vol.72, No.2, pp.205-218.
 
30.
DiMicco M.A. and Sah R.L. (2003): Dependence of cartilage matrix composition on biosynthesis, diffusion and reaction. – Transport in Porous Media, vol.50, pp. 57-73.
 
31.
Barta E. and Maroudas A. (2006): A theoretical study of the distribution of insulin-like growth factor in human articular cartilage. – J. Theor. Biology, vol.241, pp.628-638.
 
32.
Klein T.J. and Sah R.L. (2007): Modulation of depth – dependent properties in tissue – engineered cartilage with a semi-permeable membrane and perfusion: a continuum model of matrix metabolism and transport. – Biomech. Model. Mechanobiology, vol.6, pp.21-23.
 
33.
Kącki E. (1967): Thermokinetics (in Polish). –Warszawa: WN-T.
 
34.
Crank J. (1975): The Mathematic of Diffusion. – 2 nd Edition, Oxford: Clarendon Press.
 
35.
Korn G.A. and Korn T.M. (2013): Mathematical Handbook for Scientists and Engineers. – New York: Dover Publication, Inc.
 
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ISSN:1734-4492
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