Soo Hyeon Shin1, Priyanka Ghosh2, Bryan Newman2, Dana C Hammell1, Sam G Raney2, Hazem E Hassan3,4,5, Audra L Stinchcomb6,7. 1. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, 21201, USA. 2. Division of Therapeutic Performance, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA. 3. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, 21201, USA. hhassan@rx.umaryland.edu. 4. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Room: N525, Baltimore, Maryland, 21201, USA. hhassan@rx.umaryland.edu. 5. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt. hhassan@rx.umaryland.edu. 6. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, 21201, USA. astinchc@rx.umaryland.edu. 7. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Room: N521, Baltimore, Maryland, 21201, USA. astinchc@rx.umaryland.edu.
Abstract
PURPOSE: At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). METHODS: IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. RESULTS: Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The Jmax enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p < 0.05) among the three fentanyl TDSs. The Jmax enhancement ratios due to transient heat exposure were significantly different for the two nicotine TDSs, but not for the three fentanyl TDSs. Furthermore, the transient heat exposure affected the clearance of drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. CONCLUSIONS: This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.
PURPOSE: At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). METHODS: IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. RESULTS: Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The Jmax enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p < 0.05) among the three fentanyl TDSs. The Jmax enhancement ratios due to transient heat exposure were significantly different for the two nicotine TDSs, but not for the three fentanyl TDSs. Furthermore, the transient heat exposure affected the clearance of drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. CONCLUSIONS: This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.
Entities:
Keywords:
IVPT; TDS; fentanyl; heat; heat effect; in vitro permeation test; nicotine; skin permeation; temperature; transdermal delivery systems
Authors: Suneela Prodduturi; Nakissa Sadrieh; Anna M Wokovich; William H Doub; Benjamin J Westenberger; Lucinda Buhse Journal: J Pharm Sci Date: 2010-05 Impact factor: 3.534
Authors: Qian Zhang; Michael Murawsky; Terri D LaCount; Jinsong Hao; Priyanka Ghosh; Sam G Raney; Gerald B Kasting; S Kevin Li Journal: J Pharm Sci Date: 2020-07-20 Impact factor: 3.534
Authors: Terri D LaCount; Qian Zhang; Jinsong Hao; Priyanka Ghosh; Sam G Raney; Arjang Talattof; Gerald B Kasting; S Kevin Li Journal: AAPS J Date: 2020-05-10 Impact factor: 4.009