Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75(10):1119–30.

    Article  CAS  Google Scholar 

  2. Munoz R, Berry D. Dexmedetomidine: promising drug for pediatric sedation? Pediatr Crit Care Med. 2005;6(4):493–4.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  4. Gelach AT, Dasta JF. Dexmedetomidine:an updated review. Ann Pharmacother. 2007;41(2):245–52.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  14. Ratajczak H, Sobczyk L. Dipole moments of hydrogen-bonded complexes and proton-transfer effect. J Chem Phys. 1969;50(1):556–7.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  17. Mojumdar EH, Lyubartsev AP. Molecular dynamics simulations of local anesthetic articaine in a lipid bilayer. Biophys Chem. 2010;153(1):27–35.

    Article  CAS  Google Scholar 

  18. Haward RN. Occupied volume of liquids and polymers. J Macromol Sci Polym Rev. 1970;4:191–242.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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. Barry B. Mode of action of penetration enhancers in human skin. J Control Release. 1987;6(1):85–97.

    Article  CAS  Google Scholar 

  22. Kalia YN, Guy RH. Modeling transdermal drug release. Adv Drug Deliv Rev. 2001;48(2–3):159–72.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  31. Kaushik D, Michniak-Kohn B. Percutaneous penetration modifiers and formulation effects: thermal and spectral analyses. AAPS PharmSciTech. 2010;11(3):1068–83.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China

    Haiying Wang, Qi Tian, Peng Quan, Chao Liu & Liang Fang

Authors
  1. Haiying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qi Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peng Quan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liang Fang.

Ethics declarations

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Tian, Q., Quan, P. et al. 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. AAPS PharmSciTech 21, 4 (2020). https://doi.org/10.1208/s12249-019-1539-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-019-1539-0

KEY WORDS

Search

Navigation