Comparison of the complexation between methylprednisolone and different cyclodextrins in solution by 1H-NMR and molecular modeling studies.
J Pharm Sci
; 99(9): 3863-73, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20665846
ABSTRACT
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(11)) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metilprednisolona
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Beta-Ciclodextrinas
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Gama-Ciclodextrinas
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Anti-Inflamatórios
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Bélgica