INCLUSION COMPLEXATION OF GLISENTIDE WITH ALPHA-CYCLODEXTRINS, BETA-CYCLODEXTRINS AND GAMMA-CYCLODEXTRINS

Complexation of glisentide with alpha-, beta- and gamma-cyclodextrin ( CD) has been investigated in aqueous solution and in the solid state. Complex formation in solution has been analysed using solubility diagr ams and NMR spectroscopy and the interaction in solid state has been s tudied by X-ray diffractometry: DSC and IR spectroscopy. The thermodyn amic parameters, Delta H degrees, Delta S degrees and Delta G degrees, of complexation with beta- and gamma-CD have been calculated from the temperature dependence of the stability constant. The process has bee n found to be esothermic and Delta S degrees is slightly unfavourable. In addition, it has been found that the ionization state of glisentid e plays an important role in complexation and the fact that the extent of complexation is greater with beta- than with gamma-CD has revealed the importance of the cavity size to get an adequate fitting between host and guest molecules. The inclusion of the ortho-substituted aroma tic ring of glisentide has been evidenced by NMR spectroscopy. Finally , complexes have been prepared by coprecipitation and kneading methods and it has been found that the former is more suitable to achieve sol id-state complexation. (C) 1998 Elsevier Science B.V. All rights reser ved.