Advertisement

AAPS PharmSciTech

, 21:4 | Cite as

Probing the Role of Ion-Pair Strategy in Controlling Dexmedetomidine Penetrate Through Drug-in-Adhesive Patch: Mechanistic Insights Based on Release and Percutaneous Absorption Process

  • Haiying Wang
  • Qi Tian
  • Peng Quan
  • Chao Liu
  • Liang FangEmail author
Research Article

Abstract

The purpose of present study was to develop a controlled release drug-in-adhesive patch for transdermal delivery of dexmedetomidine (Dex) using ion-pair technique. Based on the in vitro transdermal experiment, the role of ion-pair on the Dex release behavior and percutaneous absorption process was also investigated. Fourier transform infrared spectroscopy (FTIR), molecular modeling, differential scanning calorimetry (DSC), and rheological test were conducted to probe the effect of ion-pair on the Dex release from patch. Besides, the tape stripping test, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and molecular simulation were carried out to elaborate the action of ion-pair on the Dex percutaneous permeation process. Results showed that the optimized patch prepared with Dex-salicylic acid (SA) showed zero-order skin permeation profile within 24 h; Dex-SA had greater hydrogen bonding formation potential with pressure sensitive adhesive (PSA) than Dex, which resulted in the decrease in the formation ability of free volume of PSA and the increase with the improvement of mechanical strength and chain stiffness of PSA and thus controlled the release rate of Dex from transdermal patch. Besides, the physicochemical properties of Dex such as molecular weight and octanol/water partition coefficient were changed after forming ion-pair with SA, which decreased the permeation ability of Dex. In conclusion, a controlled release drug-adhesive patch for Dex was developed and the mechanism study of ion-pair on the Dex release and percutaneous permeation process was proposed at molecular level.

KEY WORDS

dexmedetomidine ion-pair controlled release transdermal patch molecular mechanism 

Notes

Compliance with Ethical Standards

All animal experiments were performed according to the NIH Guidelines for the Care and Use of Laboratory Animals as well as the guidelines for animal use published by the Life Science Research Center of Shenyang Pharmaceutical University.

References

  1. 1.
    Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75(10):1119–30.CrossRefGoogle Scholar
  2. 2.
    Munoz R, Berry D. Dexmedetomidine: promising drug for pediatric sedation? Pediatr Crit Care Med. 2005;6(4):493–4.CrossRefGoogle Scholar
  3. 3.
    Candiotti KA, Bergese SD, Bokesch PM, et al. Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial. Anesth Analg. 2009;110(1):47–56.CrossRefGoogle Scholar
  4. 4.
    Gelach AT, Dasta JF. Dexmedetomidine:an updated review. Ann Pharmacother. 2007;41(2):245–52.CrossRefGoogle Scholar
  5. 5.
    Jones GM, Murphy CV, Gelach AT, et al. High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety. Ann Pharmacother. 2011;45(6):740–7.CrossRefGoogle Scholar
  6. 6.
    Hui M, Quan P, Yang Y, Fang L. The effect of ion-pair formation combined with penetration enhancers on the skin permeation of loxoprofen. Drug Deliv. 2016;23(5):1550–7.PubMedGoogle Scholar
  7. 7.
    Liu N, Song W, Song T, Fang L. Design and evaluation of a novel felbinac transdermal patch: combining ion-pair and chemical enhancer strategy. AAPS PharmSciTech. 2016;17(2):262–71.CrossRefGoogle Scholar
  8. 8.
    Song T, Quan P, Xiang R, Fang L. Regulating the skin permeation rate of escitalopram by ion-pair formation with organic acids. AAPS PharmSciTech. 2016;6(17):1267–73.CrossRefGoogle Scholar
  9. 9.
    Li Q, Wan X, Liu C, Fang L. Investigating the role of ion-pair strategy in regulating nicotine release from patch: mechanistic insights based on intermolecular interaction and mobility of pressure sensitive adhesive. Eur J Pharm Sci. 2018;119:102–11.CrossRefGoogle Scholar
  10. 10.
    Wang W, Song T, Wan X, Liu C, Zhao H, Fang L. Investigate the control release effect of ion-pair in the development of escitalopram transdermal patch using FT-IR spectroscopy, molecular modeling and thermal analysis. Int J Pharm. 2017;529(1–2):391–400.CrossRefGoogle Scholar
  11. 11.
    Zhao H, Liu C, Quan P, Wan X, Shen M, Fang L. Mechanism study on ion-pair complexes controlling skin permeability: effect of ion-pair dissociation in the viable epidermis on transdermal permeation of bisoprolol. Int J Pharm. 2017;532(1):29–36.CrossRefGoogle Scholar
  12. 12.
    Cui H, Quan P, Zhao H, et al. Mechanism of ion-pair strategy in modulating skin permeability of zaltoprofen: insight from molecular-level resolution based on molecular modeling and confocal laser scanning microscopy. J Pharm Sci. 2015;104(10):3395–403.CrossRefGoogle Scholar
  13. 13.
    Gilli P, Pretto L, Bertolasi V, Gilli G. Predicting hydrogen-bond strengths form acid-base molecular properties. The pKa slide rule: toward the solution of a long-lasting problem. Acc Chem Res. 2009;42(1):33–44.CrossRefGoogle Scholar
  14. 14.
    Ratajczak H, Sobczyk L. Dipole moments of hydrogen-bonded complexes and proton-transfer effect. J Chem Phys. 1969;50(1):556–7.CrossRefGoogle Scholar
  15. 15.
    Kim JH, Ko JA, Kim JT, et al. Preparation of a capsaicin-loaded nanoemulsion for improving skin penetration. J Agric Food Chem. 2014;62(3):725–32.CrossRefGoogle Scholar
  16. 16.
    Zhao H, Liu C, Yang D, et al. Molecular mechanism of ion-pair releasing from acrylic pressure sensitive adhesive containing carboxyl group: roles of doubly ionic hydrogen bond in the controlled release process of bisoprolol ion-pair. J Control Release. 2018;289:146–57.CrossRefGoogle Scholar
  17. 17.
    Mojumdar EH, Lyubartsev AP. Molecular dynamics simulations of local anesthetic articaine in a lipid bilayer. Biophys Chem. 2010;153(1):27–35.CrossRefGoogle Scholar
  18. 18.
    Haward RN. Occupied volume of liquids and polymers. J Macromol Sci Polym Rev. 1970;4:191–242.CrossRefGoogle Scholar
  19. 19.
    Rastogi SK, Singh J. Passive and iontophoretic transport enhancement of insulin through porcine epidermis by depilatories: permeability and Fourier transform infrared spectroscopy studies. AAPS PharmSciTech. 2003;4(3):1–9.CrossRefGoogle Scholar
  20. 20.
    Zhang CF, Yang ZL, Luo JB. Effects of enantiomer and isomer permeation enhancers on transdermal delivery of ligustrazine hydrochloride. Pharmaceutical Development and Technology. Eur J Pharm Sci. 2006;4(11):417–24.Google Scholar
  21. 21.
    Barry B. Mode of action of penetration enhancers in human skin. J Control Release. 1987;6(1):85–97.CrossRefGoogle Scholar
  22. 22.
    Kalia YN, Guy RH. Modeling transdermal drug release. Adv Drug Deliv Rev. 2001;48(2–3):159–72.CrossRefGoogle Scholar
  23. 23.
    Morimoto Y, Kokubo T, Sugibayashi K. Diffusion of drugs in acrylic-type pressure-sensitive adhesive matrix. II. Influence of interaction. J Control Release. 1992;18(2):113–22.CrossRefGoogle Scholar
  24. 24.
    Liu C, Quan P, Li S, et al. A systemic evaluation of drug in acrylic pressure sensitive adhesive patch in vitro and in vivo: the roles of intermolecular interaction and adhesive mobility variation in drug controlled release. J Control Release. 2017;252:83–94.CrossRefGoogle Scholar
  25. 25.
    Li N, Wan X, Quan P, et al. Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes. Eur J Pharm Sci. 2017;107:138–47.CrossRefGoogle Scholar
  26. 26.
    Dimas DA, Dallas PP, Rekkas DD, et al. Effect of several factors on the mechanical properties of pressure-sensitive adhesives used in transdermal therapeutic systems. AAPS PharmSciTech. 2000;1(2):80–7.PubMedCentralGoogle Scholar
  27. 27.
    Puttipipatkhachorn S, Nunthanid J, et al. Drug physical state and drug-polymer interaction on drug release from chitosan matrix films. J Control Release. 2001;75(1–2):143–53.CrossRefGoogle Scholar
  28. 28.
    Weerheim A, Ponec M. Determination of stratum corneum lipid profile by tape stripping in combination with high-performance thin-layer chromatography. Arch Dermatol Res. 2001;293(4):191–9.CrossRefGoogle Scholar
  29. 29.
    Hoppel M, Baurecht D, Holper E, et al. Validation of the combined ATR-FTIR/tape stripping technique for monitoring the distribution of surfactants in the stratum corneum. Int J Pharm. 2014;472(1–2):88–93.CrossRefGoogle Scholar
  30. 30.
    Salimi A, Hedayatipour N, Moghimipour E. The effect of various vehicles on the naproxen permeability through rat skin: a mechanistic study by DSC and FT-IR techniques. Adv Pharm Bull. 2016;6(1):9–16.CrossRefGoogle Scholar
  31. 31.
    Kaushik D, Michniak-Kohn B. Percutaneous penetration modifiers and formulation effects: thermal and spectral analyses. AAPS PharmSciTech. 2010;11(3):1068–83.CrossRefGoogle Scholar
  32. 32.
    Chen Y, Cun D, Quan P, et al. Saturated long-chain esters of isopulegol as novel permeation enhancers for transdermal drug delivery. Pharm Res. 2014;31(8):1907–18.CrossRefGoogle Scholar
  33. 33.
    Sanders JC, Haris PI, et al. Secondary structure of M13 coat protein in phospholipids studied by circular dichroism, Raman, and Fourier transform infrared spectroscopy. Biochemistry. 1993;32(46):12446–54.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Haiying Wang
    • 1
  • Qi Tian
    • 1
  • Peng Quan
    • 1
  • Chao Liu
    • 1
  • Liang Fang
    • 1
    Email author
  1. 1.Department of Pharmaceutical SciencesShenyang Pharmaceutical UniversityShenyangChina

Personalised recommendations