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

Purpose. The objective of the study was to obtain structural information of inclusion complexes of tolbutamide with HP-alpha- and -beta-cyclodextrins in amorphous state. Method. 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 C-13 nucle ar magnetic resonance (NMR) spectroscopy. Results. The solid 1:1 and 1:2 tolbutamide/HP-CyD complexes showed halo pat tern on the powder X-ray diffractogram and no thermal change in DSC curves, indicating they are in an amorphous state. C-13 NMR signals of the butyl m oiety were broader than those of the phenyl moiety in the HP-alpha-CyD soli d complex, whereas the phenyl moiety showed significantly broader signals t han the butyl moiety in the HP-beta-CyD solid complex. As temperature incre ased, signals of the phenyl carbons became markedly sharper, whereas the bu tyl carbons only sharpen slightly in the HP-d-CyD complex. In contrast, sig nals of the butyl carbons became significantly sharper whereas those of phe nyl carbons only slightly changed in the HP-beta-CyD complex. Conclusions. Solid state C-13 NMR spectroscopic studies indicated that the butyl moiety of tolbutamide is predominantly included in the HP-alpha-CyD c avity, whereas the phenyl moiety in the HP-beta-CyD cavity in amorphous com plexes.