Skip to main content
SpringerLink
Log in

Solubilization of cyclosporin A

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

This study investigated the solubilization of cyclosporin A (CsA), a neutral undecapeptide, by cosolvency, micellization, and complexation. Cosolvents (ethanol, propylene glycol, polyethylene glycol, tetrahydrofurfuryl alcohol polyethyleneglycol ether, and glycerin), surfactants (polyoxyethylene sorbitan monooleate [(Tween 80)], polyoxyethylene sorbitan monolaurate [(Tween 20)], and Cremophor EL), and cyclodextrins (α-cyclodextrin [(αCD)] and hydroxypropyl-β-cyclodextrin[(HP\CD)] were used as solubilizing agents in this study.

Surfactants had a noticeable effect in increasing CsA solubility. Twenty percent solutions of Tween 20, Tween 80, and Cremophor EL increased the solubility by 60 to 160 fold. Cyclodextrins can increase the CsA solubility, but αCD was more effective than HP\CD. Cosolvents on the other hand did not increase the solubility of CsA as much as expected from the LOGP (logrithm of wateroctanol partition coefficent) value of CsA.

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

Similar content being viewed by others

Refrences

  1. Petcher TJ, Weder HP, Rüegger A. Crystal and molecular structure of an iodo derivative of the cyclic undecapeptide cyclosporin A.Helvetica Chimica Acta. 1976;59:1480–1488.

    Article  CAS  Google Scholar 

  2. Alfred F. Cyclosporin clinical pharmacokinetics.Drug Dispos. 1993;24:472–495.

    Google Scholar 

  3. Ismailos G, Peppas C, Dressman J, Macheras P. Unusual solubility behavior of cyclosporin A in aqueous media.J Pharm Pharmacol. 1991;43:287–289.

    CAS  Google Scholar 

  4. Yalkowsky SH.Solubility and Solubilization in Aqueous Media. New York, NY: Oxford University Press; 1999.

    Google Scholar 

  5. Yalkowsky SH, Roseman TJ. Solubilization of drugs by cosolvents. In:Techniques of Solubilization of Drugs. New York, NY: Dekker; 1981.

    Google Scholar 

  6. Yalkowsky SH, Rubino JT. Solubilization of cosolvents 1: organic solutes in propylene glyco-water mixtures.J Pharm Sci. 1985;74:416–421.

    Article  CAS  Google Scholar 

  7. Zhao L, Li P, Yalkowsky SH. Solubilization of fluasterone.J Pharm Sci. 1999;88:967–969.

    Article  CAS  Google Scholar 

  8. Attwood D, Florence AT.Surfactant Systems. New York, NY: Chapman and Hall; 1983.

    Google Scholar 

  9. Connors KA, Mollica JA. Theoretical analysis of comparative studies of complex formation: solubility, spectral, and kinetic techniques.J Pharm Sci. 1966;55:772–780.

    Article  CAS  Google Scholar 

  10. Loftsson T, Brewster ME. Pharmaceutical application of cyclodextrins. 1. Drug solubilization and stabilization.J Pharm Sci. 1996;85:1017–1025.

    Article  Google Scholar 

  11. Gilbert BE, Wilson SZ, Garcon NM, Wyde PR, Knight V. Characterization and administration of cyclosporine liposomes as a small-particle aerosol.Transplantation. 1993;56:974–977.

    Article  CAS  Google Scholar 

  12. El Tayar N, Mark AE, Vallat P, Brunne RM, Testa B, van Gunsteren WF. Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: evidence from partition coefficients and molecular dynamics simulations.J Med Chem. 1993;36:3757–3764.

    Article  Google Scholar 

  13. Kessler H, Gehrke M, Lautz J, Kock M, Seebach D, Thaler A. Complexation and medium effects on the conformation of cyclosporin A studied by NMR spectroscopy and molecular dynamics calculations.Biochem Pharmacol. 1990;40:169–173.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences; College of Pharmacy, The University of Arizona, 1703 Mabel Street, 85721, Tucson, AZ

    Yingqing Ran & Samuel H. Yalkowsky

  2. Aventis Pharmaceuticals Company, 08807, Bridgewater, NJ

    Luwei Zhao

  3. Department of Chemistry, The University of Arizona, 85721, Tucson, AZ

    Qing Xu

Authors
  1. Yingqing Ran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luwei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Samuel H. Yalkowsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yingqing Ran.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ran, Y., Zhao, L., Xu, Q. et al. Solubilization of cyclosporin A. AAPS PharmSciTech 2, 2 (2001). https://doi.org/10.1208/pt020102

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1208/pt020102

KeyWords

Search

Navigation