Available on ORBi since
17 December 2009
Article (Scientific journals)
The Effect of Cyclodextrins on the Aqueous Solubility of a New Mmp Inhibitor: Phase Solubility, 1 H-Nmr Spectroscopy and Molecular Modeling Studies, Preparation and Stability Study of Nebulizable Solutions
Bertholet, Pascal; Guéders, Maud  ; Dive, Georges  et al.
2005 • In Journal of Pharmacy and Pharmaceutical Sciences, 8 (2), p. 164-175
Peer Reviewed verified by ORBi
 

Files


Full Text
The effect of cyclodextrins on the aqueous solubility of a new..._Bertholet_05_JPharmPharmSci.pdf
Publisher postprint (1.39 MB)

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] PURPOSE: Ro 28-2653 (RO) is a synthetic inhibitor of matrix metalloproteinases (MMPs), which is potentially effective against bronchial remodeling. Given that this molecule has very poor aqueous solubility, different cyclodextrins (CDs) have been tested to increase its solubility. The aim of this study was to prepare and to characterize inclusion complexes between RO and CDs, in order to develop nebulizable solutions. METHODS: The complex formation was investigated by phase solubility studies. (1)H-NMR spectroscopy and molecular modeling studies were carried out to elucidate the structure of the inclusion complex between RO and dimethyl-beta-CD (DIMEB). Nebulizable solutions of RO were developed with CDs and a stability study was performed over 9 months. RESULTS: The phase solubility studies showed that beta-CD and its derivatives form a 1:2 complex with RO, whereas gamma-CD includes RO with a 1:1 stoichiometry and a weak stability constant. T-ROESY spectra showed that DIMEB is able to complex two RO substituents (nitrophenyl and biphenyl groups) with preferential orientations, while molecular modeling demonstrated that the configurations observed with (1)H-NMR are energetically favorable, especially owing to H-bond formation between RO and DIMEB. Two CDs were selected to develop nebulizable solutions of RO and the stability study demonstrated that RO degradation in solution is strongly dependent on the concentration of the 1:2 inclusion complex. CONCLUSIONS: CDs are able to include RO and to improve its aqueous solubility. The beta-CD derivatives can be used to formulate nebulizable solutions of RO, the stability of which depends on the concentration of the 1:2 complex.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Bertholet, Pascal
Guéders, Maud ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Dive, Georges ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Albert, Adelin ;  Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Barillaro, Valery
Perly, Bruno
Cataldo, Didier  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques
Piel, Géraldine ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique et magistrale
Delattre, Luc ;  Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Evrard, Brigitte  ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Language :
English
Title :
The Effect of Cyclodextrins on the Aqueous Solubility of a New Mmp Inhibitor: Phase Solubility, 1 H-Nmr Spectroscopy and Molecular Modeling Studies, Preparation and Stability Study of Nebulizable Solutions
Publication date :
2005
Journal title :
Journal of Pharmacy and Pharmaceutical Sciences
eISSN :
1482-1826
Publisher :
Canadian Society for Pharmaceutical Sciences, Canada
Volume :
8
Issue :
2
Pages :
164-175
Peer reviewed :
Peer Reviewed verified by ORBi

Statistics


Number of views
58 (16 by ULiège)
Number of downloads
4 (4 by ULiège)

Scopus citations®
 
5
Scopus citations®
without self-citations
3

Bibliography


Similar publications



Contact ORBi