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![]() J. Biomedical Science and Engineering, 2010, 3, 367-374 JBiSE doi:10.4236/jbise.2010.34051 Published Online April 2010 (http://www.SciRP.org/journal/jbise/). Published Online April 2010 in SciRes. http://www.scirp.org/journal/jbise Transdermal drug delivery models Grantham K. H. Pang, Da-Peng Qiao Department of Electrical and Electronic Engineering, University of Hong Kong, Hong Kong, China. Email: gpang@eee.hku.hk Received 12 January 2010; revised 25 January 2010; accepted 9 February 2010. ABSTRACT In this paper, a preliminary study based on the different models of the skin impedance is carried out. The purpose is to examine the drug delivery method through iontophoresis, which relies on active trans- portation of the charged medication agent within an electric field. It is a kind of transdermal drug delivery method, and hence the method has to handle the variability in skin characteristics of a patient. This paper carries out a simulation study based on three different skin impedance models. Keywords: Target Drug Delivery; Biomedical Engineering; Skin Impedance; Iontophoresis 1. INTRODUCTION Nowadays, as opposed to the traditional oral intake and hypodermal injection, drug delivery to a patient can be carried out in many different ways. Transdermal drug delivery releases the medicament into the patient’s body via the skin. There are various methods for transdermal drug delivery and they have been developed based on various principles. The developed methods could be based on diffusion, absorption, thermal energy, radio frequency energy, ultrasound, electrostatic force (elec- trophoresis) or electric field (iontophoresis). These are non-invasive methods, and recent developments also include transdermal skin patch that is placed on the skin to deliver a specific dose of medication through the skin, and then into the blood stream of the patient. The main advantage of a transdermal drug delivery is that it provides a controlled release of the medicament without serious pain to the patient. However, all transdermal drug delivery methods have to deal with the complicated properties of the patient’ skin, which is a very effective barrier, and its character- istics can vary a lot from one person to another. It is a natural barrier to foreign chemicals and biological agents. Methods that are based on the use of microneedles [1-3] have also been developed. These microneedles would physically puncture the skin but for less than 1 mm and deliver the drug without piercing blood vessels or dam- aging nerves, that are typically around 1 mm under the skin surface. The mechanical stability and the punc- ture behaviour of microneedles have been investigated experimentally [3]. In this paper, several electrical models for skin impedance are investigated and simulations have been carried out for a comparative study of the parameters for drug delivery through iontophoresis [4,5]. 2. METHOD AND ANALYSIS 2.1. Introduction Research has found that skin impedance can be modeled by typical RC (resistor-capacitor) circuits, without the need of any inductive component [6-9]. Hence, it is gen- erally agreed that the skin impedance is made up of some amount of resistance and some form of capacitance. Different models of RC circuits can be developed to simulate current responses in actual skin. 2.2. Model A An early skin impedance model is given in [7] and it is shown in Figure 1. The model is made up of a capacitor C in parallel with the resistance R1. R1 is modeling the resistance of the stratum corneum, which is the top layer of the epidermis. C represents the capacitance of the skin. The C-R1 parallel combination is in series with another resistance R2 which represents the resistance of the deeper tissues within the epidermis. Example of value for R1 would range from around 100 Ω to 5000 kΩ cm2, while R2 would range from around 0.1 Ω to 1.0 kΩ cm2. Figure 1. Skin impedance Model A. ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 368 This model is simple and can serve as an initial repre- sentation to the skin characteristics. However, a more complete representation is given in the next subsection. 2.3. Model B Another model can also be found in [8] by Tregear which is consisted of multiple parallel RC circuits in series. This is designed to model the varying capacitance and resistance of the epidermal skin layers at different depths of the skin. This model is shown in Figure 2 be- low. As mentioned in [5], this model represents the de- creasing values of capacitance and resistance as individ- ual layers of the stratum corneum are removed in ex- periments. The experimental result was important as it allows for the development of a more precise model of the skin impedance. Also, it has shown that the stratum corneum accounts for the major portion of the skin im- pedance in the skin. 2.4. Model C Lykken [9] has proposed another model of skin imped- ance as shown in Figure 3. The model consists of sev- eral parallel paths, and each path is made up of several RC circuits, with each circuit representing a different layer of the skin. Figure 3 provides a more distributed nature when modeling the skin impedance, and can po- tentially provide a more accurate model. Figure 2. Skin impedance Model B. Figure 3. Skin impedance Model C. 3. RESULTS AND SIMULATION In this section, simulations based on the three skin impedance models discussed in the previous section are presented. In these simulations, a voltage is ap- plied at time 0.1 second and it varies linearly to 5 V at time 0.5 second. 3.1. Simulation Based on Model A Several simulations have been carried out to examine the characteristics of the responses that may be obtained based on different parameter values. For the purpose of simulation, R1 and R2 have been assigned a value of 100 kΩ cm2 and three different values of the capacitor have been used. Below are the results from the simulation: It can be seen from the simulation that as the voltage is increased from 0.1 second to 0.5 second, the current passes through the capacitor C of Model A. At 0.5 second, the applied voltage has already reached the final value, and the current passes through R1 and R2. For all the three simulations, the final steady-state current depends on the value of the two resistors. As shown in Figures 4 to 6, the value of the capacitor can have considerable effect on the shape of the response. 3.2. Simulation Based on Model B In the first simulation of Model B, we will examine the re- sponse from Level 1. The capacitance value is 0.1 μF cm2. Figure 8 gives the current for Model B having only three sections (Level 1). This would model after three epidermal skin layers at different depths of the skin. ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 369 Figure 9 gives the current for Model B having six sections (Level 2). More sections (or skin layers) can be included for further study, but in this paper, we show the simulations of only Level 1 and 2. As shown in Figures 8 and 10, the current can have very different response at different point of the circuit model. In both cases, the current would settle down to its steady-state level very quickly after the voltage has been steady at 0.5 second. Figure 4. Model A with capacitor value 1 μF cm2. Figure 5. Model A with capacitor value 10 μF cm2. ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 370 Figure 6. Model A with capacitor value 100 μF cm2. Figure 7. Level 1 of Model B. Figure 8. Model B level 1 with capacitor value 0.1 μF cm2. ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 371 Figure 9. Level 2 of Model B. Figure 10. Model B level 2 with capacitor value 0.1 μF cm2. 3.3. Simulation Based on Model C In Figure 11, Model C with three parallel paths is shown. Each path is consisted of three sub-sections. Figures 12 and 15 are similar in shape but differ in its vertical scale. Hence, although these two results are based on different circuit models (3 sub-section and 6 sub-section model), similar response shapes are obtained with the use of different capacitor values. The vertical scales can be aligned with a careful choice of the resistor values. 4. CONCLUSIONS The three-element circuit of Model A is a very simple model of the skin impedance. Considering the different characteristics to the different layer of the epidermis, the model seems not too accurate in its representation. The Model B by Tregear captures the effects of capacitance for the different layers of the epidermis. However, it is not clear how many stages should best represent the skin Figure 11. Model C with three parallel paths, each with three sub-sections. ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 372 Figure 12. Simulation result of Model C with three parallel paths, each with three sub-sections, with ca- pacitor value 100 μF cm2, R1 = 1000 Ω cm2, R2 = 100 Ω cm2. Figure 13. Model C with three parallel paths, each with six sub-sections. ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 373 Figure 14. Simulation result of Model C with three parallel paths, each with six sub-sections, with capacitor value 10 μF cm2, R1 = 1000 Ω cm2, R2 = 100 Ω cm2. Figure 15. Simulation result of Model C with three parallel paths, each with six sub-sections, with capacitor value 100 μF cm2, R1 = 1000 Ω cm2, R2 = 100 Ω cm2. impedance for a certain depth of the epidermis. The Model C by Lykken has added another resistance in between the different stage, which is used to represent deep tissue resistance. This would provide a more complete model to the skin impedance. Yet, the great variability of the parameters in the model exists and experimentally study is needed for a more complete understanding of the impedance characteristics of the ![]() G. K. H. Pang et al. / J. Biomedical Science and Engineering 3 (2010) 367-374 Copyright © 2010 SciRes. JBiSE 374 skin. 5. ACKNOWLEDGEMENTS This research is supported by a Small Project Funding grant (10400021) by the Committee on Research and Conference Grants of The University of Hong Kong. REFERENCES [1] Stoebar, B. and Liepmann, D. (2005) Array of hollow out-of-plane microneedles for drug delivery. Journal of MEMS, 14(3), 474-479. [2] Ji, J., Tay, F.E.H., Miao, J. and Iliescu, C. (2006) Micro- fabricated microneedles with porous tip for drug delivery. Journal of Micromechanics and Microengineering, 16, 958- 964. [3] Lam, D.C.C., Lee, Y.H., Shek, K.T. and Pang, G. (2008) Puncture depth and the mechanical stability of micro- needles. International Joint Conference on Biomedical Engineering Systems and Technologies, 2, 291-296. [4] Coston, A.F. and Li, J.K.-J. (2001) Iontophoresis: Model- ling, methodology, and evaluation. Cardiovascular En- gineering, 1, 127-136. [5] Coston, A.F. and Li, J.K.-J. (2003) Transdermal drug delivery: A comparative analysis of skin impedance mo- dels and parameters. Proceedings of IEEE Engineering in Medicine and Biology, 3, 2982-2985. [6] Lawler, J.C., Davis, M.J. and Griffith, E.C. (1960) Elec- trical characteristics of the skin: The impedance of the surface sheath and deep tissues. Journal of Investigative Dermatology, 34, 301-308. [7] Edelberg, R. (1971) Electrical properties of skin. In El- den, H.R. Ed., Biophysical properties of the skin, John Wiley & Sons, Inc, New York. [8] Tregear, R.T. (1966) Physical functions of the skin. Aca- demic Press, New York. [9] Lykken, D.T. (1970) Square-wave analysis of skin im- pedance. Psychophysiology, 7(2), 262-275. |