Investigation and physicochemical characterization of clarithromycin-citric acid-cyclodextrins ternary complexes.
The purpose of this study was to investigate the effect of citric acid (CA) on the complexation of clarithromycin (CLM) with beta-cyclodextrin (betaCD) in aqueous solutions and in the solid state. A phase solubility study revealed a positive effect of CA on the drug solubility. A B(s)-type solubility with an apparent stability constant (K(c)) of 102.4 M(-1) was obtained for CLM in betaCD solution and 161.2 M(-1) for CLM in 6 mM betaCD solution. Solid ternary complexes were prepared by coevaporation and lyophilization. CLM-betaCD-CA interactions were studied in the solid state by differential scanning calorimetry (DSC), infrared spectroscopy, scanning electron microscopy and X-ray diffractometry. A part of the guest molecule was located in the betaCD host cavity. The results obtained suggest that the lyophilization method yields a higher degree of amorphous entity than coevaporation.
Zhang
Xiangrong
X
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang, PR China.
Zhang
Yifan
Y
Zhong
Dafang
D
Chen
Ying
Y
Li
Sanming
S
D000900:Anti-Bacterial Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002627:Chemistry, Physical / Q000379:methods*; D002845:Chromatography / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid / Q000737:chemistry*; D017291:Clarithromycin / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D047392:beta-Cyclodextrins; D019343:Citric Acid; D017291:Clarithromycin; C031215:betadex