[en] The ability of cyclodextrins (CDs) to increase the solubility of cyproterone acetate (CPA) was previously shown by phase-solubility and NMR studies [1]. In the present work, the influence of various CDs on the stability of CPA was studied in pH 6 and pH 8 aqueous solutions at 25degreesC. Different CDs were tested: hydroxypropyl-beta-cyclodextrin (HPbetaCD), randomly methylated beta-cyclodextrin (RAMEB), hydroxypropyl-gamma-cyclodextrin (HPgammaCD) and gamma-cyclodextrin (gammaCD). At pH 6, the presence of these CDs reduces the degradation of CPA. Nevertheless, at pH 8, the gamma-CD derivatives are ineffective against the degradation of CPA, whereas the beta-CD derivatives (HPbetaCD and RAMEB) allow decreasing CPA hydrolysis. Molecular modeling was performed to theoretically calculate some of the most energetically favorable conformations for gamma-CD and RAMEB complexes with CPA. The position of the ester group in the CD caivity seems to be the most important factor influencing the hydrolysis of CPA. Other factors, such as the size of the cavity, the substitution of the CD hydroxyls and the stability constant also have a strong incidence on CPA stability.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Henry de Hassonville, Sandrine
Dive, Georges ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Barillaro, Valery
Bertholet, Pascal
Delattre, Luc ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Piel, Géraldine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique et magistrale
Language :
English
Title :
Application of molecular modeling to the study of cyproterone acetate stability in the presence of cyclodextrin derivatives
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