Skip to main content

Advertisement

SpringerLink
Log in

The Control of Skin-Permeating Rate of Bisoprolol by Ion-Pair Strategy for Long-Acting Transdermal Patches

  • Rapid Communication
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

A moderate drug permeating rate (flux) is desirable for long-acting transdermal patches. In this work, a novel simple method of controlling bisoprolol (BSP) flux by ion-pair strategy was initiated. Different ion-pair complexes including bisoprolol maleate (BSP-M), bisoprolol tartarate, bisoprolol besilate, and bisoprolol fumarate were prepared and their fluxes through rabbit abdominal skin were determined separately in vitro. Furthermore, permeation behavior from isopropyl myristate, solubility index in pressure-sensitive adhesives, determined by DSC, and n-octanol/water partition coefficient (log P) were investigated to illustrate the mechanism of drug permeation rate controlling. The results showed that compared to free BSP (J = 25.98 ± 2.34 μg/cm2/h), all BSP ion-pair complexes displayed lower and controllable flux in the range of 0.11 to 4.19 μg/cm2/h. After forming ion-pair complexes, the capability of BSP to penetrate through skin was weakened due to the lowered log P and increased molecule weight. Accordingly, this study has demonstrated that the flux of BSP could be controlled by ion-pair strategy, and among all complexes investigated, BSP-M was the most promising candidate for long-acting transdermal patches.

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

References

  1. Czuriga I, Riecansky I, Bodnar J, Fulop T, Kruzsicz V, Kristof E, et al. Comparison of the new cardioselective beta-blocker nebivolol with bisoprolol in hypertension: the Nebivolol, Bisoprolol Multicenter Study (NEBIS). Cardiovasc Drugs Ther. 2003;17:257–63.

    Article  PubMed  CAS  Google Scholar 

  2. Zhao JH, Fu JH, Wang SM, Su CH, Shan Y, Kong SJ, et al. A novel transdermal patch incorporating isosorbide dinitrate with bisoprolol: in vitro and in vivo characterization. Int J Pharm. 2007;337:88–101.

    Article  PubMed  CAS  Google Scholar 

  3. Kim J, Shin SC. Controlled release of atenolol from the ethylene-vinyl acetate matrix. Int J Pharm. 2004;273:23–7.

    Article  PubMed  CAS  Google Scholar 

  4. Zhan XP, Chen SJ, Tang GC, Mao ZM. Poly (2-hydroxy-3- phenoxypropylacrylate, 4-hydroxybutyl acrylate, dibutyl maleate) membrane controlled clonidine zero-order release. Eur J Pharm Biopharm. 2007;66:429–34.

    Article  PubMed  CAS  Google Scholar 

  5. Mukherjeea B, Mahapatraa S, Guptab R, Patraa B, Tiwari A, Arorab P. A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation. Eur J Pharm Biopharm. 2005;59:475–83.

    Article  Google Scholar 

  6. Hadgraft J, Walters KA, Wotton RK. Facilitated percutaneous absorption: a comparison and evaluation of two in vitro models. Int J Pharm. 1986;32:257–63.

    Article  CAS  Google Scholar 

  7. Cheong HA, Choi HK. Enhanced percutaneous absorption of piroxicam via salt formation with ethanolamines. Pharm Res. 2002;19:1375–80.

    Article  PubMed  CAS  Google Scholar 

  8. Nam SH, Xu YJ, Nam H, Jin GW, Jeong Y, An S, et al. Ion pairs of risedronate for transdermal delivery and enhanced permeation rate on hairless mouse skin. Int J Pharm. 2011;419:114–20.

    Article  PubMed  CAS  Google Scholar 

  9. Ren CS, Fang L, Li T, Wang ML, Zhao LG, He ZG. Effect of permeation enhancers and organic acids on the skin permeation of indapamide. Int J Pharm. 2008;350:43–7.

    Article  PubMed  CAS  Google Scholar 

  10. Zhao LG, Li Y, Fang L, He ZG, Liu XT, Wang L, et al. Transdermal delivery of tolterodine by O-acylmenthol: in vitro/in vivo correlation. Int J Pharm. 2009;374:73–81.

    Article  PubMed  CAS  Google Scholar 

  11. Li CM, Liu C, Liu J, Fang L. Correlation between rheological properties, in vitro release, and percutaneous permeation of tetrahydropalmatine. AAPS PharmSciTech. 2011;12:1002–10.

    Article  PubMed  CAS  Google Scholar 

  12. Fang L, Numajiri S, Kobayashi D, Morimoto Y. The use of complexation with alkanolamines to facilitate skin permeation of mefenamic acid. Int J Pharm. 2003;262:13–22.

    Article  PubMed  CAS  Google Scholar 

  13. Sato K, Mitsui N, Hasegawa T, Sugibayashi K, Morimoto Y. Potential usefulness of solubility index for prediction of the skin permeation rate of 5-ISMN from pressure-sensitive adhesive tape. J Control Release. 2001;73:269–77.

    Article  PubMed  CAS  Google Scholar 

  14. Ma X, Fang L, Guo GP, Zhao NX, He ZG. Effect of counter-ions and penetration enhancers on the skin permeation of flurbiprofen. J Pharm Sci. 2009;99:1826–37.

    Google Scholar 

  15. Magnusson BM, Anissimov YG, Cross SE, Roberts MS. Molecular size as the main determinant of solute maximum flux across the skin. J Invest Dermatol. 2004;122:993–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Wenting Song, Dongmei Cun, Honglei Xi & Liang Fang

Authors
  1. Wenting Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dongmei Cun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Honglei Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liang Fang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, W., Cun, D., Xi, H. et al. The Control of Skin-Permeating Rate of Bisoprolol by Ion-Pair Strategy for Long-Acting Transdermal Patches. AAPS PharmSciTech 13, 811–815 (2012). https://doi.org/10.1208/s12249-012-9808-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-012-9808-1

Key words

Search

Navigation