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Evaluation of Heat Effects on Transdermal Delivery Systems Using In Vitro Permeation Test Strategy

Zhang, Qian
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505123897155412

Abstract Details

2017, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
Many transdermal delivery systems (TDS) exhibit altered performance under conditions of elevated temperature, which may lead to unanticipated toxicity and drug dosing complications. Currently, there is no standard in vitro test method to evaluate and compare the performance of TDS under the influence of elevated temperature. Therefore, the objective of this dissertation was to develop an experimental model to evaluate heat effects on drug delivery from TDS in vitro. First of all, experiments were performed in humans and in Franz diffusion cells with human cadaver skin to record skin and TDS temperatures at room temperature and with heat exposure. Skin temperatures were regulated with two methods: a heating lamp in vivo and in vitro, or thermostatic control of the receiver chamber in vitro. The in vivo-in vitro correlation which was built based on the relationship between temperature measurements and thermal resistances identified the heating lamp method as an adequate heat application method to be used with an in vitro permeation test (IVPT) strategy for studying heat effects on TDS. This IVPT method was then tested on two drugs, nicotine and fentanyl TDS, to determine the effects of heat on TDS flux under different heat application time regimens. The nicotine study was investigated from two commercial TDS (Alza and Aveva) while the fentanyl study was conducted on three commercial TDS (Alza, Aveva, and Mylan). The activation energies for both nicotine and fentanyl were obtained by conducting skin permeation experiments without TDS in side-by-side diffusion cells under 32°C and 42°C. In addition to the IVPT strategy, a separately developed computational heat-and-mass transport model was also employed to characterize key transport parameters, thereby providing mechanistic insight into heat-enhanced TDS drug delivery. The 10°C increase in skin surface temperature resulted in a ~1.8-fold and a ~2.0-fold flux increase for the studied nicotine and fentanyl TDS, respectively. The increase in flux at 42°C was consistent with the activation energy (EA) for skin permeation reported in the literature for permeants of similar molecular sizes and lipophilicities as well as the experimental EA values in the present skin permeation study without the TDS. Moreover, higher flux was observed when heat was applied earlier or with sustained heat application. In addition, model predictions for various heat application times were in agreement with the corresponding IVPT data of both nicotine and fentanyl TDS. In conclusion, the combination of in vitro and computational models could provide a valuable approach to measure heat effects on TDS delivery.
Kevin Li, Ph.D. (Committee Chair)
Jiukuan Hao, Ph.D. (Committee Member)
Jinsong Hao, Ph.D. (Committee Member)
Gerald Kasting, Ph.D. (Committee Member)
Harshita Kumari, Ph.D. (Committee Member)
155 p.
Pharmaceuticals

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Citations

  • Zhang, Q. (2017). Evaluation of Heat Effects on Transdermal Delivery Systems Using In Vitro Permeation Test Strategy [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505123897155412

    APA Style (7th edition)

  • Zhang, Qian. Evaluation of Heat Effects on Transdermal Delivery Systems Using In Vitro Permeation Test Strategy. 2017. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505123897155412.

    MLA Style (8th edition)

  • Zhang, Qian. "Evaluation of Heat Effects on Transdermal Delivery Systems Using In Vitro Permeation Test Strategy." Doctoral dissertation, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505123897155412

    Chicago Manual of Style (17th edition)

ucin1505123897155412
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© 2017, some rights reserved.Creative Commons License Evaluation of Heat Effects on Transdermal Delivery Systems Using In Vitro Permeation Test Strategy by Qian Zhang is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.