Phase solubility and structure of the inclusion complexes of prednisolone and 6α-methyl prednisolone with various cyclodextrins

✍ Scribed by Kim L. Larsen; Finn L. Aachmann; Reinhard Wimmer; Valentino J. Stella; Ulrich Madsen Kjølner

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 138 KB
• Volume: 94
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20192

✦ Synopsis

The purpose of this work was to study the inclusion binding interaction of two structurally related steroids, prednisolone and 6a-methyl prednisolone with a wide variety of cyclodextrins (CDs), both native (a-, b-and g-CD) as well as modified (hydroxypropyl-, sulfobutyl ether-, glucosyl-, and maltosyl-b-CD and sulfobutyl etherg-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 (K 1:1 ) revealed that b-CD formed the strongest complex with prednisolone, followed by g-CD. With 6a-methyl prednisolone, the stability constants of both b-and a-CD were considerably lower compared with prednisolone. In contrast, g-CD formed a stronger complex with 6a-methyl prednisolone compared with prednisolone. Derivatives of b-CD gave slightly altered stability constants compared with native b-CD. The structures of the complexes between the two guest molecules and native b-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 6amethyl 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.