AAPS PharmSciTech

, 4:1 | Cite as

Synergistic effect of PEG-400 and cyclodextrin to enhance solubility of progesterone

  • Indranil Nandi
  • Michelle Bateson
  • Mohammad Bari
  • Hemant N. Joshi


PEG-400, polysorbate 80, and 2 CDs (Trappsol HPB and Captisol) were used in an attempt to improve the aqueous solubility of a model hydrophobic drug, progesterone. The aqueous solubility of progesterone improved significantly from 0.007 mg/mL by the addition of PEG-400, CDs, and polysorbate 80. In systems containing various amounts of PEG-400 and 3% Trappsol HPB in water (% wt/wt), the theoretical solubility was calculated by adding the solubilities in the individual systems. The observed solubility values were up to 96% higher than the theoretical values. The effect of synergism was significant in 5% to 50% PEG-400/water systems containing Trappsol HPB. Systems containing Captisol did not show such synergistic effects. In general, the addition of polysorbate 80 to the PEG-400/water systems containing CDs affected synergism negatively.


cosolvent cyclodextrins PEG-400 progesterone solubilization synergism 


  1. 1.
    Loftsson T, Brewster ME. Pharmaceutical application of cyclodextrin: drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–1025.PubMedCrossRefGoogle Scholar
  2. 2.
    Wulff M, Alden M. Solid state studies of drug—cyclodextrin inclusion complexes in PEG 6000 prepared by a new method. Eur J Pharm. 1999;8:269–281.CrossRefGoogle Scholar
  3. 3.
    Harada A. Preparation and structures of supramolecules between cyclodextrins and polymers. Coordin Chem Rev. 1996;148:115–133.CrossRefGoogle Scholar
  4. 4.
    Loftsson T, Olafsdottir BJ, Fridriksdottir H, Jonsdottir S. Cyclodextrin complexations of NSAIDs: physicochemical characteristics. Eur J Pharm Sci. 1993;1:95–101.CrossRefGoogle Scholar
  5. 5.
    Savolainen J, Jarvinen K, Taipale H, Jarho P, Loftsson T, Jarvinen T. Co-administration of a water-soluble polymer increases the usefulness of cyclodextrins in solid dosage forms. Pharm Res. 1998;15:1696–1701.PubMedCrossRefGoogle Scholar
  6. 6.
    Loftsson T, Petersen DS. Cyclodextrin solubilization of ETH-615, a zwitterionic drug. Drug Dev Ind Pharm. 1998;24:365–370.PubMedCrossRefGoogle Scholar
  7. 7.
    Loftsson T, Gudmundsdottir H, Sigurjonsdottir JF, et al. Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray. Int J Pharm. 2001;212:29–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Zung JB. Influence of alcohol addition on the γ-CD:pyrene complex. J Phys Chem. 1991;95:6701–6709.CrossRefGoogle Scholar
  9. 9.
    Pitha J, Hoshino T. Effect of ethanol on formation of inclusion complexes of hydroxypropylcyclodextrins with testosterone or with methyl orange. Int J Pharm. 1992;80:243–251.CrossRefGoogle Scholar
  10. 10.
    Faucci MT, Mura P. Effect of water-soluble polymers on naproxen complexation with natural and chemically modified β-cyclodextrins. Drug Dev Ind Pharm. 2001;27:909–917.PubMedGoogle Scholar
  11. 11.
    Li P, Zhao L, Yalkowsky SH. Combined effect of cosolvent and cyclodextrin on solubilization of nonpolar drugs. J Pharm Sci. 1999;88:1107–1111.PubMedCrossRefGoogle Scholar
  12. 12.
    Martin A. Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences. Philadelphia, PA: Lea and Febiger, 1993:223.Google Scholar
  13. 13.
    Millard JW, Alvarex-Nunez FA, Yalkowsky SH. Solubilization by cosolvents—establishing useful constants for the log-linear model. Int J Pharm. 2002;245:153–166.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2003

Authors and Affiliations

  • Indranil Nandi
    • 1
  • Michelle Bateson
    • 2
  • Mohammad Bari
    • 3
  • Hemant N. Joshi
    • 4
  1. 1.Geneva Pharmaceutical Technology CorpDayton
  2. 2.Galen LimitedLarneNorthern Ireland
  3. 3.Forest Laboratories IncInwood
  4. 4.Barr LaboratoriesPharmaceutical Research & DevelopmentPomona

Personalised recommendations