Phase solubility and structure of the inclusion complexes of prednisolone and 6 alpha-methyl prednisolone with various cyclodextrins.
The purpose of this work was to study the inclusion binding interaction of two structurally related steroids, prednisolone and 6alpha-methyl prednisolone with a wide variety of cyclodextrins (CDs), both native (alpha-, beta- and gamma-CD) as well as modified (hydroxypropyl-, sulfobutyl ether-, glucosyl-, and maltosyl-beta-CD and sulfobutyl ether-gamma-CD), and to relate the binding constants to structural differences in the steroids. Phase-solubility diagrams of the steroids with various CDs were obtained. The stability constants (K1:1) revealed that beta-CD formed the strongest complex with prednisolone, followed by gamma-CD. With 6alpha-methyl prednisolone, the stability constants of both beta- and alpha-CD were considerably lower compared with prednisolone. In contrast, gamma-CD formed a stronger complex with 6alpha-methyl prednisolone compared with prednisolone. Derivatives of beta-CD gave slightly altered stability constants compared with native beta-CD. The structures of the complexes between the two guest molecules and native beta-CD were studied by nuclear magnetic resonance spectroscopy. This clearly showed that the introduction of the methyl group led to a different binding geometry of 6alpha-methyl prednisolone compared with prednisolone. Additionally, the nuclear magnetic resonance results indicate the presence of an additional, weaker binding site, which is less populated in prednisolone.
Larsen
Kim L
KL
Institute of Life Sciences, University of Aalborg, Sohngaardsholmsvej 49/57, DK9000 Aalborg, Denmark. kll@bio.au.dk
Aachmann
Finn L
FL
Wimmer
Reinhard
R
Stella
Valentino J
VJ
Kjølner
Ulrich Madsen
UM
D003505:Cyclodextrins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000737:chemistry*; D044367:Phase Transition; D011239:Prednisolone / Q000737:chemistry*; D012995:Solubility / Q000187:drug effects; D013816:Thermodynamics
D003505:Cyclodextrins; D011239:Prednisolone; C078007:methylprednisolone aceponate; D008775:Methylprednisolone