Structural evaluation of crystalline ternary γ-cyclodextrin complex.
The 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 (13) C 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.
Higashi
Kenjirou
K
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, chuo-ku, Chiba 260-8675, Japan. ken-h@p.chiba-u.ac.jp
Ideura
Saori
S
Waraya
Haruka
H
Moribe
Kunikazu
K
Yamamoto
Keiji
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D005079:Excipients / Q000737:chemistry*; D005480:Flurbiprofen / Q000737:chemistry*; D007660:Ketoprofen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009288:Naproxen / Q000737:chemistry; D010592:Pharmaceutic Aids / Q000737:chemistry; D033362:Powder Diffraction; D020156:Salicylic Acid / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000032:analysis; D047408:gamma-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D010592:Pharmaceutic Aids; D047408:gamma-Cyclodextrins; D014867:Water; D009288:Naproxen; D005480:Flurbiprofen; D007660:Ketoprofen; D020156:Salicylic Acid