Solid-State Preparation of Inclusion Compounds of Native Cyclodextrins with Diclofenac Sodium

Inclusion compounds of diclofenac sodium, a non-steroidal anti-inflammatory drug, with native α-, β- and γ-cyclodextrins at varying levels of hydration were prepared by co-grinding in a ball mill. Using TG/DSC analysis, powder X-ray diffraction and solid-state IR spectroscopy, it was shown that when equimolar mixtures of native cyclodextrin and diclofenac are milled, complete inclusion of this pharmaceutical ingredient occurs, regardless of cyclodextrin hydration. The absence of water-guest competition in the solid-state inclusion process is explained by high affinity of diclofenac sodium to cyclodextrins. The prepared complexes have a significantly lower thermal stability than the separate native cyclodextrins and diclofenac sodium.