Complexation of the interferon inducer, bropirimine, with hydroxypropyl-beta-cyclodextrin

Bropirimine (ABPP) is an orally active immunomodulator that increases endog enous alpha-interferon and other cytokines used clinically against carcinom a in situ of the bladder. The oral absorption of ABPP is poor because its l ow solubility in water. The purpose of this study is to develop a technolog ical procedure useful to increase the water solubility of ABPP. To this end , the interaction of ABPP with several cyclodextrin derivatives-alpha-, bet a-, gamma- and hydroxypropyl-beta-cyclodextrin with a degree of substitutio n 2.7 (HP beta CD) was studied and the effect of the complexation process o n the water solubility of the drug was evaluated. The best results were obt ained with the hydroxypropyl derivative, HP beta CD, that interacts in a 1: 1 drug:cyclodextrin molar ratio. The inclusion complex ABPP-HP beta CD was characterized in solution by nuclear magnetic resonance (H-1 -NMR). The sol id inclusion complex was obtained by freeze-drying and characterized by dif ferential scanning calorimetry (DSC), X-ray diffractometry and mass spectro metry. The dissolution rate of ABPP from the HP beta CD solid inclusion com plex was increased compared to the powdered drug but not differences were f ound between the complex and a physical mixture with a similar molar ratio. The increase of the dissolution rate of the drug can be attributed to the breakdown in solution of the drug dimers in the presence of the cyclodextri n and to the complex formation. (C) 2000 Elsevier Science B.V. All rights r eserved.