Structural Evaluation of Crystalline Ternary γ-Cyclodextrin Complex

ABSTRACTThe structure of a crystalline γ-cyclodextrin (γ-CD) ternary complex containing salicylic acid (SA) and flurbiprofen (FBP) prepared by sealed heating was investigated. FBP/γ-CD inclusion complex was prepared by coprecipitation; its molar ratio was determined as 1/1. Powder X-ray diffraction measurements showed that the molecular packing of γ-CD changed from hexagonal to monoclinic columnar form by sealed heating of SA with dried FBP/γ-CD inclusion complex, indicating ternary complex formation. The stoichiometry of SA/FBP/γ-CD was estimated as 2/1/1. Solid-state transformation of γ-CD molecular packing upon water vapor adsorption and desorption was irreversible for this ternary complex, in contrast to the reversible transition for the FBP/γ-CD inclusion complex. The ternary complex contained one FBP molecule in the cavity of γ-CD and two SA molecules in the intermolecular space between neighboring γ-CD column stacks. Infrared and 13C solid-state NMR spectroscopies revealed that the molecular states of SA and FBP changed upon ternary complex formation. In the complex, dimer FBP molecules were sandwiched between two γ-CD molecules whereas each monomer SA molecule was present in the intermolecular space of γ-CD. Ternary complex formation was also observed for other drug-guest systems using naproxen and ketoprofen. Thus, the complex can be used to formulate variety of drugs.