Hygroscopicity, phase solubility and dissolution of various substituted sulfobutylether beta-cyclodextrins (SBE) and danazol-SBE inclusion complexes.
The aim of the present work was to characterize hygroscopicity, phase solubility and dissolution properties for various substituted sulfobutylether beta-cyclodextrins (SBEs) and danazol-SBE inclusion complexes. Moisture sorption was measured using a symmetric gravimetric analyzer. The complexes were characterized by powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Moisture sorption isotherms for the SBEs and the complexes showed low moisture sorption at RH <60%. The moisture absorption desorption isotherms for the various SBEs showed very little hysteresis, indicating almost complete desorption. Moisture adsorbed by the various SBE was in the order SBE 7>SBE 4>SBE 5 at 95% RH. Powder XRD data for complexes showed the disappearance of characteristic crystalline peaks for danazol or the formation of amorphous entities and DSC showed the disappearance of the peak of fusion of danazol indicating complex formation. Phase solubility of danazol with various substituted SBEs indicated 1:1 stoichiometry of complexes. The apparent stability constant, as determined by the method of Higuchi and Connors, increased as the degree of substitution of SBEs increased and decreased as the temperature increased. The dissolution of the complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of poorly soluble danazol. More than 85% of danazol was released in <10 min, compared to 15% danazol release from the physical mixtures.
Jain
A C
AC
Graduate School of Pharmaceutical Sciences, Duquesne University, 441 Mellon Hall, Pittsburgh, PA 15282, USA.
Adeyeye
M C
MC
D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D003613:Danazol / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D017155:Wettability; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D003613:Danazol