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-beta-cyclodextrin (HP-beta-CD), gamma-cyclodextrin (gamma-CD), and 2-hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD)] was studied using phase solubility analysis, one and two-dimensional (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: gamma-CD > HP-gamma-CD > HP-beta-CD. The large variation of chemical shifts from protons located around the interior of the hydrophobic cavity (H-3', H-5', and H-6') coupled with minimal variation of shifts from protons located on the outer sphere of gamma-CD (H-1', H-2', and H-4') provided clear evidence of inclusion complexation. The molecular modeling study, indicated inclusion complexation between methylprednisolone and gamma-CD and HP-gamma-CD by entrance of the A and B rings of methylprednisolone into the CD cavity from its bigger rim. For the methylprednisolone: HP-beta-CD complex, the molecular modeling study could not be carried out; hence, two possibilities of complex formation are proposed: (1) methylprednisolone enters HP-beta-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.
Thi
Thao Do
TD
Laboratory for Pharmacotechnology and Biopharmacy, KU Leuven, Belgium.
Nauwelaerts
Koen
K
Froeyen
Matheus
M
Baudemprez
Luc
L
Van Speybroeck
Michiel
M
Augustijns
Patrick
P
Annaert
Pieter
P
Martens
Johan
J
Van Humbeeck
Jan
J
Van den Mooter
Guy
G
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008775:Methylprednisolone / Q000737:chemistry*; D008958:Models, Molecular; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C031215:betadex; D008775:Methylprednisolone