Assessment of solid-state interactions of naproxen with amorphous cyclodextrin derivatives by DSC

A microcalorimetric method based on differential scanning calorimetry (DSC) of drug-additive binary systems to assess kneading-induced interactions was applied to naproxen (NAP) in combinations with amorphous hydroxypropyl β-cyclodextrin (HPβCd), β-cyclodextrin sulfobutyl ether, sodium salt ((SBE) 7m-βCd), acetyl β-cyclodextrin (AcβCd) and acetyl γ-cyclodextrin (AcγCd). Modifications of thermal parameters of NAP in DSC curves of physical mixtures indicate heating-induced interactions which resulted in a broadening of the NAP melting endotherm in the combinations with HPβCd, AcβCd and AcγCd. The effect of kneading on the interaction was particularly pronounced for the NAP–HPβCd and NAP–(SBE) 7m-βCd systems, which show a similar drug-to-carrier interaction ratio (1:2 by weight) as that of the other systems. Drug-to-carrier ratios, calculated considering the amount of NAP which recrystallizes from the melted mixtures equivalent to NAP not bound to the carrier, show a distinctly lower affinity in solid-state of the drug for the anionically charged (SBE) 7m-βCd with respect to other neutral carriers. The similar affinity of NAP for AcβCd and AcγCd demonstrates that the geometry of the cavity, which is a determinant factor for the inclusion complexation in liquid state, does not influence the interaction process in solid-state.