INTERACTIONS OF KETOPROFEN AND IBUPROFEN WITH BETA-CYCLODEXTRINS IN SOLUTION AND IN THE SOLID-STATE

The complexing, solubilizing and amorphizing abilities towards ketopro fen and ibuprofen of native beta-cyclodextrin and some randomly substi tuted amorphous derivatives (methyl, hydroxyethyl, and hydroxypropyl b eta-cyclodextrin with an average substitution degree per anhydroglucos e unit, respectively of 1.8, 1.6 and 0.9) were determined and compared with those already observed for naproxen. Drug-carrier interactions w ere studied in aqueous solution by means of phase-solubility analysis and C-13 NMR spectroscopy, and in the solid state using differential s canning calorimetry (DSC), X-ray powder diffractometry and infrared sp ectroscopy. The strength of the inclusion complexes with beta-cyclodex trins (K-1:1,K-ibu, K-1:1,K-nap > K-1:1,K-keto) was directly related t o the hydrophobic character of the guest (log P values) and depended o n its molecular features. The presence in physical mixtures of a high- energy state of crystalline drug molecularly dispersed in the amorphou s carrier was assumed from DSC, behaviour. Dissolution rates (disperse d amount method) of the active ingredient from equimolar drug-cyclodex trin physical mixtures and amorphous colyophilized products showed tha t methyl beta-cyclodextrin was the most effective carrier also for ket oprofen and ibuprofen. (C) 1998 Elsevier Science B.V. All rights reser ved.