Reference : The Effect of Cyclodextrins on the Aqueous Solubility of a New Mmp Inhibitor: Phase Solu...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
http://hdl.handle.net/2268/2376
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
English
Bertholet, Pascal [> > > >]
Guéders, Maud mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Dive, Georges mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Albert, Adelin mailto [Université de Liège - ULg > Département des sciences de la santé publique > Informatique médicale et biostatistique >]
Barillaro, Valery [> > > >]
Perly, Bruno [> > > >]
Cataldo, Didier mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques]
Piel, Géraldine mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique et magistrale >]
Delattre, Luc mailto [Université de Liège - ULg > Département de pharmacie > Département de pharmacie >]
Evrard, Brigitte mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
2005
Journal of Pharmacy & Pharmaceutical Sciences : A Publication of the Canadian Society for Pharmaceutical Sciences
8
2
164-175
Yes (verified by ORBi)
International
1482-1826
[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.
http://hdl.handle.net/2268/2376
http://www.ualberta.ca/~csps/JPPS8(2)/jourcont8(2).htm

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