Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats

Caglar Macit; Gülengül Duman; Meltem Macit

Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats

Abstract

Recently, transdermal drug delivery has become popular due to their numerous advantages. They offer non-invasive application and eliminate the first-pass metabolism. The skin membrane is sensitive to heat and vibration that these applications enhance the skin permeability resulting in increased bioavailability. This study aims to determine the effect of steam bath (STB), vibration (VIB) and thermal ablation (THAB) on systemic absorption of tramadol HCl and compare all applications with each other. After preparing of tramadol HCl patches, in vitro release tests followed by in vivo animal experiments were conducted. The patches were applied to 32 Wistar albino rats divided into four groups: No potential trigger effect (NPTE), STB, VIB, and THAB. STB, VIB and THAB were applied by purchased devices. One hour later, the patches were removed and plasma concentration of tramadol HCl was measured by UV-Vis spectrophotometry at 271 nm. When compared to the control group, calculated plasma tramadol HCl µg/mL concentration increased significantly in STB, VIB and THAB (p<0.001). Finally, as trigger effects, steam bath, vibration and thermal ablation (42°C) dramatically increased the absorption amount of tramadol HCl (42.1%, 37.2 % and 43.8 %, respectively). The percentage release of tramadol HCl increased significantly in investigation groups when compared to NPTE (p<0.001). In conclusion, controlled heat and vibration applications are effective in the enhancement of transdermal drug absorption.

Keywords

References

[1] Varshosaz J, Faghihian H, Rastgoo K. Preparation and characterization of metoprolol controlled-release solid dispersions. Drug Deliv. 2006; 13(4): 295-302. https://doi.org/10.1080/10717540500459308
[2] Mohamed HM, Mahmoud AM. Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats. Biomed Pharmacother. 2019; 110: 239-247. https://doi.org/10.1016/j.biopha.2018.11.141
[3] Pozos-Guillén Ade J, Martínez-Rider R, Aguirre-Bañuelos P, Arellano-Guerrero A, Hoyo-Vadillo C, Pérez-Urizar J. Analgesic efficacy of tramadol by route of administration in a clinical model of pain. Proc West Pharmacol Soc. 2005; 48: 61-64.
[4] Bal SM, Ding Z, van Riet E, Jiskoot W, Bouwstra JA. Advances in transcutaneous vaccine delivery: do all ways lead to Rome?. J Control Release. 2010; 148(3): 266-282. https://doi.org/10.1016/j.jconrel.2010.09.018
[5] Lee JW, Gadiraju P, Park JH, Allen MG, Prausnitz MR. Microsecond thermal ablation of skin for transdermal drug delivery. J Control Release. 2011; 154(1): 58-68. https://doi.org/10.1016/j.jconrel.2011.05.003
[6] Rathore GS, Basniwal PK, Suthar M, Gupta RN. Spectrophotometric estimation of tramadol hydrochloride in pharmaceutical dosage forms. Asian J. Chem. 2009; 21(8): 6111-5.
[7] Precision Microdrives Limited. https://www.precisionmicrodrives.com/vibration-motors/coin-vibration-motors/ (accessed 05 May 2019).
[8] US Food and Drug Administration, FYs 2013 - 2017 GDUFA Science and Research Report: Transdermal Drug Products, 2018, https://www.fda.gov/ForIndustry/UserFees/GenericDrugUserFees/ucm605293.htm (accessed 25 July 2023).

[9] Verma P, Thakur AS, Deshmukh K, Jha AK, Verma S. ROUTES OF DRUG ADMINISTRATION, IJPSR. 2010; 1(8): 54-59.
[10] Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P, Stinchcomb AL. Challenges and opportunities in dermal/transdermal delivery. Ther Deliv. 2010; 1(1): 109-131. https://doi.org/10.4155/tde.10.16
[11] Patel R, Patel A, Prajapati B, Shinde G, Dharamsi A. Transdermal drug delivery systems: a mini review. Int. J. of Adv. Res. 2018; 6: 891–900. http://dx.doi.org/10.21474/IJAR01/7109
[12] Ammar HO, Ghorab M, El-Nahhas SA, Kamel R. Polymeric matrix system for prolonged delivery of tramadol hydrochloride, part I: physicochemical evaluation. AAPS PharmSciTech. 2009; 10(1): 7-20. https://doi.org/10.1208/s12249-009-9294-2
[13] Economidou SN, Lamprou DA, Douroumis D. 3D printing applications for transdermal drug delivery. Int J Pharm. 2018; 544(2): 415-424. https://doi.org/10.1016/j.ijpharm.2018.01.031
[14] Long LY, Zhang J, Yang Z, Guo Y, Hu X, Wang Y. Transdermal delivery of peptide and protein drugs: strategies, advantages and disadvantages. JDDST. 2020; 60: 102007. https://doi.org/10.1016/j.jddst.2020.102007
[15] Shingade GM, Aamer Quazi, Sabale PM, Grampurohit ND, Gadhave MV, Jadhav SL, Gaikwad DD. Review on: Recent Trend on Transdermal Drug Delivery System. JDDT. 2012; 2(1): 66-75. https://doi.org/10.22270/jddt.v2i1.74
[16] Anselmo AC, Gokarn Y, Mitragotri S. Non-invasive delivery strategies for biologics. Nat Rev Drug Discov. 2019; 18(1): 19-40. https://doi.org/10.1038/nrd.2018.183
[17] Johnson JM, Jr. Kellogg DR. Thermoregulatory and thermal control in the human cutaneous circulation, Frontiers in bioscience Scholar edT. 2010; 2: 825–853. https://doi.org/10.2741/S105
[18] Minson CT, Berry LT, Joyner MJ. Nitric oxide and neurally mediated regulation of skin blood flow during local heating. J Appl Physiol (1985). 2001; 91(4): 1619-1626. https://doi.org/10.1152/jappl.2001.91.4.1619
[19] Selsby JT, Dodd SL. Heat treatment reduces oxidative stress and protects muscle mass during immobilization. Am J Physiol Regul Integr Comp Physiol. 2005; 289(1): R134-R139. https://doi.org/10.1152/ajpregu.00497.2004
[20] Park JH, Lee JW, Kim YC, Prausnitz MR. The effect of heat on skin permeability. Int J Pharm. 2008; 359(1-2): 94-103. https://doi.org/10.1016/j.ijpharm.2008.03.032
[21] Yun J, Lee DH, Im JS, Kim HI. Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater. Mater Sci Eng C Mater Biol Appl. 2012; 32(6): 1564-1570. https://doi.org/10.1016/j.ijpharm.2008.03.032
[22] Kim KS, Simon L. Modeling and design of transdermal drug delivery patches containing an external heating device. Comput. Chem. Eng. 2011; 35(6): 1152-1163. https://doi.org/10.1016/j.compchemeng.2011.01.006
[23] Wood DG, Brown MB, Jones SA. Controlling barrier penetration via exothermic iron oxidation. Int J Pharm. 2011; 404(1-2): 42-48. https://doi.org/10.1016/j.ijpharm.2010.10.047
[24] Petersen KK, Rousing ML, Jensen C, Arendt-Nielsen L, Gazerani P. Effect of local controlled heat on transdermal delivery of nicotine. Int J Physiol Pathophysiol Pharmacol. 2011; 3(3): 236-242.
[25] Shomaker TS, Zhang J, Ashburn MA. Assessing the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system. Pain Med. 2000; 1(3): 225-230. https://doi.org/10.1046/j.1526-4637.2000.00030.x
[26] Shin SH, Yu M, Hammell DC, Ghosh P, Raney SG, Hassan HE, Stinchcomb AL. Evaluation of in vitro/in vivo correlations for three fentanyl transdermal delivery systems using in vitro skin permeation testing and human pharmacokinetic studies under the influence of transient heat application. J Control Release. 2022; 342: 134-147. https://doi.org/10.1016/j.jconrel.2021.11.030
[27] Prodduturi S, Sadrieh N, Wokovich AM, Doub WH, Westenberger BJ, Buhse L. Transdermal delivery of fentanyl from matrix and reservoir systems: effect of heat and compromised skin. J Pharm Sci. 2010; 99(5): 2357-2366. https://doi.org/10.1002/jps.22004
[28] Gazerani P, Arendt-Nielsen L. Cutaneous vasomotor reactions in response to controlled heat applied on various body regions of healthy humans: evaluation of time course and application parameters. Int J Physiol Pathophysiol Pharmacol. 2011; 3(3): 202-209.
[29] Bernabei GF. (2006): US20067083580.
[30] Lee CA, Baek JS, Kwag DG, Lee HJ, Park J, Cho CW. Enhancement of skin permeation of vitamin C using vibrating microneedles. Transl Clin Pharmacol. 2017; 25(1): 15-20. https://doi.org/10.12793/tcp.2017.25.1.15
[31] Liu TT, Chen K, Wang Q. Skin drug permeability and safety through a vibrating solid micro-needle system. Drug Deliv Transl Res. 2018; 8(5): 1025-1033. https://doi.org/10.1007/s13346-018-0544-2
[32] Chitryniewicz-Rostek J, Nastałek M, Krężałek P, Jędrychowska D, Totko-Borkusewicz N, Uher I, Kaško D, Tota Ł, Tyka A, Tyka A, Piotrowska A. The Impact of Vibration Therapy Interventions on Skin Condition and Skin Temperature Changes in Young Women with Lipodystrophy: A Pilot Study. Evidence-based complementary and alternative medicine. 2019: 8436325. https://doi.org/10.1155/2019/8436325
[33] Sintov AC, Krymberk I, Daniel D, Hannan T, Sohn Z, Levin G. Radiofrequency-driven skin microchanneling as a new way for electrically assisted transdermal delivery of hydrophilic drugs. J Control Release. 2003; 89(2): 311-320. https://doi.org/10.1016/S0168-3659(03)00123-8
[34] Ward L, Wright E, McMahon SB. A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain. Pain. 1996; 64(1): 129-138. https://doi.org/10.1016/0304-3959(95)00080-1
[35] Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum. Pharmaceutics. 2015; 7(4): 438-70. https://doi.org/10.3390/pharmaceutics7040438
[36] Hussain A, Wahab GMKA, ur Rahman MAS, Altaf H, Akhtar N, Qayyum MI. Potential Enhancers for Transdermal Drug Delivery: A Review. Inter. J. Basic Med. Sci. Pharm. 2014; 4: 19–22.
[37] Parhi R, Mandru A. Enhancement of skin permeability with thermal ablation techniques: concept to commercial products. Drug Deliv Transl Res. 2021; 11(3): 817-841. https://doi.org/10.1007/s13346-020-00823-3
[38] Arora A, Prausnitz MR, Mitragotri S. Micro-scale devices for transdermal drug delivery. Int J Pharm. 2008; 364(2): 227-236. https://doi.org/10.1016/j.ijpharm.2008.08.032
[39] Badkar AV, Smith AM, Eppstein JA, Banga AK. Transdermal delivery of interferon alpha-2B using microporation and iontophoresis in hairless rats. Pharm Res. 2007; 24: 1389–95. https://doi.org/10.1007/s11095-007-9308-2
[40] Artzi O, Koren A, Niv R, Mehrabi JN, Friedman O. The Scar Bane, Without the Pain: A New Approach in the Treatment of Elevated Scars: Thermomechanical Delivery of Topical Triamcinolone Acetonide and 5-Fluorouracil. Dermatol Ther (Heidelb). 2019; 9(2): 321-326. https://doi.org/10.1007/s13555-019-0298-x
[41] Bachhav YG, Heinrich A, Kalia YN. Using laser microporation to improve transdermal delivery of diclofenac: Increasing bioavailability and the range of therapeutic applications. Eur J Pharm Biopharm. 2011; 78(3): 408-14. https://doi.org/10.1016/j.ejpb.2011.03.006
[42] Ashburn MA, Ogden LL, Zhang J, Love G, Basta SV. The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat. J Pain. 2003; 4(6): 291-7. https://doi.org/10.1016/s1526-5900(03)00618-7
[43] Andrews SN, Jeong E, Prausnitz MR. Transdermal delivery of molecules is limited by full epidermis, not just stratum corneum. Pharm. Res. 2013; 30: 1099-109.
[44] Reagan-Shaw S, Nihal M, Ahma, N. Dose translation from animal to human studies revisited. FASEB J. 2008; 22: 659–661. https://doi.org/10.1016/j.ijpharm.2018.01.031
[45] Sobajima M, Nozawa T, Shida T, Ohori T, Suzuki T, Matsuki A, Inoue H. Repeated steam bath therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium. Am J Physiol Heart Circ Physiol. 2011; 301(2): H548-54. https://doi.org/10.1152/ajpheart.00103.2011

Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Research Article

Authors

Caglar Macit This is me
0000-0002-5532-2395
Türkiye

Gülengül Duman ^*
0000-0002-4289-1759
Türkiye

Meltem Macit
0000-0001-9925-2387
Türkiye

Publication Date

June 28, 2025

Submission Date

June 1, 2023

Acceptance Date

September 9, 2023

Published in Issue

Year 2023 Volume: 27 Number: 5

IZ

https://izlik.org/JA76NH83LC

Cite

RIS / Bibtex

APA

Macit, C., Duman, G., & Macit, M. (2025). Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats. Journal of Research in Pharmacy, 27(5), 2171-2181. https://izlik.org/JA76NH83LC

AMA

1.Macit C, Duman G, Macit M. Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats. J. Res. Pharm. 2025;27(5):2171-2181. https://izlik.org/JA76NH83LC

Chicago

Macit, Caglar, Gülengül Duman, and Meltem Macit. 2025. “Steam Bath, Vibration, and Thermal Ablation Administrations Augment the Release of Tramadol HCl from Transdermal Patch and Enhance the Plasma Concentration in Rats”. Journal of Research in Pharmacy 27 (5): 2171-81. https://izlik.org/JA76NH83LC.

EndNote

Macit C, Duman G, Macit M (July 1, 2025) Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats. Journal of Research in Pharmacy 27 5 2171–2181.

IEEE

[1]C. Macit, G. Duman, and M. Macit, “Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats”, J. Res. Pharm., vol. 27, no. 5, pp. 2171–2181, July 2025, [Online]. Available: https://izlik.org/JA76NH83LC

ISNAD

Macit, Caglar - Duman, Gülengül - Macit, Meltem. “Steam Bath, Vibration, and Thermal Ablation Administrations Augment the Release of Tramadol HCl from Transdermal Patch and Enhance the Plasma Concentration in Rats”. Journal of Research in Pharmacy 27/5 (July 1, 2025): 2171-2181. https://izlik.org/JA76NH83LC.

JAMA

1.Macit C, Duman G, Macit M. Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats. J. Res. Pharm. 2025;27:2171–2181.

MLA

Macit, Caglar, et al. “Steam Bath, Vibration, and Thermal Ablation Administrations Augment the Release of Tramadol HCl from Transdermal Patch and Enhance the Plasma Concentration in Rats”. Journal of Research in Pharmacy, vol. 27, no. 5, July 2025, pp. 2171-8, https://izlik.org/JA76NH83LC.

Vancouver

1.Caglar Macit, Gülengül Duman, Meltem Macit. Steam bath, vibration, and thermal ablation administrations augment the release of tramadol HCl from transdermal patch and enhance the plasma concentration in rats. J. Res. Pharm. [Internet]. 2025 Jul. 1;27(5):2171-8. Available from: https://izlik.org/JA76NH83LC