Interactions of ketoprofen and ibuprofen with β-cyclodextrins in solution and in the solid state

Abstract The complexing, solubilizing and amorphizing abilities towards ketoprofen and ibuprofen of native β -cyclodextrin and some randomly substituted amorphous derivatives (methyl, hydroxyethyl, and hydroxypropyl β -cyclodextrin with an average substitution degree per anhydroglucose unit, respectively of 1.8, 1.6 and 0.9) were determined and compared with those already observed for naproxen. Drug-carrier interactions were studied in aqueous solution by means of phase-solubility analysis and 13 C NMR spectroscopy, and in the solid state using differential scanning calorimetry (DSC), X-ray powder diffractometry and infrared spectroscopy. The strength of the inclusion complexes with β -cyclodextrins ( K 1:1,ibu > K 1:1,nap > K 1:1,keto ) was directly related to the hydrophobic character of the guest (log  P values) and depended on its molecular features. The presence in physical mixtures of a high-energy state of crystalline drug molecularly dispersed in the amorphous carrier was assumed from DSC behaviour. Dissolution rates (dispersed amount method) of the active ingredient from equimolar drug-cyclodextrin physical mixtures and amorphous colyophilized products showed that methyl β -cyclodextrin was the most effective carrier also for ketoprofen and ibuprofen.