Comparison of the complexation between methylprednisolone and different cyclodextrins in solution by 1H-NMR and molecular modeling studies

✍ Scribed by Thao Do Thi; Koen Nauwelaerts; Matheus Froeyen; Luc Baudemprez; Michiel Van Speybroeck; Patrick Augustijns; Pieter Annaert; Johan Martens; Jan Van Humbeeck; Guy Van den Mooter

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 400 KB
• Volume: 99
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.22227

✦ Synopsis

Complexation in solution between methylprednisolone and three different cyclodextrins [2-hydroxypropyl-b-cyclodextrin (HP-b-CD), g-cyclodextrin (g-CD), and 2-hydroxypropyl-g-cyclodextrin (HP-g-CD)] was studied using phase solubility analysis, one and twodimensional 1 H-NMR and molecular modeling. Estimates of the complex formation constant (K 1:1 ) show that the tendency of methylprednisolone to complex with CDs follows the order: g-CD > HP-g-CD > HP-b-CD. The large variation of chemical shifts from protons located around the interior of the hydrophobic cavity (H-3 0 , H-5 0 , and H-6 0 ) coupled with minimal variation of shifts from protons located on the outer sphere of g-CD (H-1 0 , H-2 0 , and H-4 0 ) provided clear evidence of inclusion complexation. The molecular modeling study, indicated inclusion complexation between methylprednisolone and g-CD and HP-g-CD by entrance of the A and B rings of methylprednisolone into the CD cavity from its bigger rim. For the methylprednisolone: HP-b-CD complex, the molecular modeling study could not be carried out; hence, two possibilities of complex formation are proposed: (1) methylprednisolone enters HP-b-CD from the wider rim by its D and C ring, (2) the A and B ring of methylprednisolone enters deeper in to the CD cavity so that a part of the A ring of steroidal structure is outside of the cavity.