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

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 1H-NMR and molecular modeling. Estimates of the complex formation constant (K1:1) 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-30, H-50, and H-60) coupled with minimal variation of shifts from protons located on the outer sphere of g-CD (H-10, H-20, and H-40) 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.