AAPS PharmSciTech

, Volume 2, Issue 1, pp 23–26 | Cite as

Solubilization of cyclosporin A

  • Yingqing Ran
  • Luwei Zhao
  • Qing Xu
  • Samuel H. Yalkowsky


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.


Cyclosporin A Conformation Solubility Solubilization 


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  1. 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.CrossRefGoogle Scholar
  2. 2.
    Alfred F. Cyclosporin clinical pharmacokinetics.Drug Dispos. 1993;24:472–495.Google Scholar
  3. 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.Google Scholar
  4. 4.
    Yalkowsky SH.Solubility and Solubilization in Aqueous Media. New York, NY: Oxford University Press; 1999.Google Scholar
  5. 5.
    Yalkowsky SH, Roseman TJ. Solubilization of drugs by cosolvents. In:Techniques of Solubilization of Drugs. New York, NY: Dekker; 1981.Google Scholar
  6. 6.
    Yalkowsky SH, Rubino JT. Solubilization of cosolvents 1: organic solutes in propylene glyco-water mixtures.J Pharm Sci. 1985;74:416–421.CrossRefGoogle Scholar
  7. 7.
    Zhao L, Li P, Yalkowsky SH. Solubilization of fluasterone.J Pharm Sci. 1999;88:967–969.CrossRefGoogle Scholar
  8. 8.
    Attwood D, Florence AT.Surfactant Systems. New York, NY: Chapman and Hall; 1983.Google Scholar
  9. 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.CrossRefGoogle Scholar
  10. 10.
    Loftsson T, Brewster ME. Pharmaceutical application of cyclodextrins. 1. Drug solubilization and stabilization.J Pharm Sci. 1996;85:1017–1025.CrossRefGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  • Yingqing Ran
    • 1
  • Luwei Zhao
    • 2
  • Qing Xu
    • 3
  • Samuel H. Yalkowsky
    • 1
  1. 1.Department of Pharmaceutical Sciences; College of PharmacyThe University of ArizonaTucson
  2. 2.Aventis Pharmaceuticals CompanyBridgewater
  3. 3.Department of ChemistryThe University of ArizonaTucson

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