Solid-state 13C nuclear magnetic resonance spectroscopic study on amorphous solid complexes of tolbutamide with 2-hydroxypropyl-alpha- and -beta-cyclodextrins.

Abstract

The objective of the study was to obtain structural information of inclusion complexes of tolbutamide with HP-alpha- and -beta-cyclodextrins in amorphous state. The solid complexes of tolbutamide with HP-alpha- and -beta-CyDs in molar ratios of 1:1 and 1:2 (guest:host) were prepared by the spray-drying method, and their interactions were investigated by solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. The solid 1:1 and 1:2 tolbutamide/HP-CyD complexes showed halo pattern on the powder X-ray diffractogram and no thermal change in DSC curves, indicating they are in an amorphous state. 13C NMR signals of the butyl moiety were broader than those of the phenyl moiety in the HP-alpha-CyD solid complex, whereas the phenyl moiety showed significantly broader signals than the butyl moiety in the HP-beta-CyD solid complex. As temperature increased, signals of the phenyl carbons became markedly sharper, whereas the butyl carbons only sharpen slightly in the HP-d-CyD complex. In contrast, signals of the butyl carbons became significantly sharper whereas those of phenyl carbons only slightly changed in the HP-beta-CyD complex. Solid state 13C NMR spectroscopic studies indicated that the butyl moiety of tolbutamide is predominantly included in the HP-alpha-CyD cavity, whereas the phenyl moiety in the HP-beta-CyD cavity in amorphous complexes.