Effect of beta-cyclodextrin on the degradation rate of amoxicillin in acidic solution.
The formation of an inclusion complex of amoxicillin (AMX) with beta-cyclodextrin (beta-CD) in aqueous solution was confirmed by a solubility method and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The apparent stability constant for the inclusion complex was 10.72 M(-1) in water at 25 degrees C. The effect of alpha-CD, beta-CD, and gamma-CD on the degradation of AMX in a pH 1.2 solution at 37 degrees C was investigated. beta-CD and gamma-CD reduced the rate of degradation. alpha-CD had no effect. These results were consistent with those of 1H-NMR spectroscopy. The effect of beta-CD on the degradation rate was studied in more detail. The apparent first order rate constant for the degradation of AMX in the pH 1.2 solution at 37 degrees C was 0.1121 h(-1) (t(1/2)=6.18 h), which decreased with the addition of beta-CD. The rate constants and t(1/2) values for the concentrations of beta-CD added, corresponding to molar ratios of AMX to beta-CD of 1:0.5, 1:1, 1:2, 1:5, and 1:10, were 0.1051 h(-1) and 6.59 h, 0.0992 h(-1) and 6.98 h, 0.0893 h(-1) and 7.76 h, 0.0697 h(-1) and 9.95 h, and 0.0509 h(-1) and 13.61 h, respectively. The activation energy for the degradation of AMX in the pH 1.2 solution was increased from 6.9 x 10(4) J/mol (AMX alone) to 8.0 x 10(4) J/mol (AMX:beta-CD=1:10).
College of Pharmacy, Nihon University.
Shinji
S
Hidaka
Tadakazu
T
Tokumura
Kazuo
K
Tomono
Toyofumi
T
Suzuki
Haruhisa
H
Ueda
Tsuneji
T
Nagai
Masashi
M
Nagaoka
Rieko
R
Nakane
Yoshiharu
Y
Machida
D000143:Acids; D000658:Amoxicillin; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility; D012996:Solutions; D013696:Temperature; D014867:Water; D047392:beta-Cyclodextrins
D000143:Acids; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; D000658:Amoxicillin; C031215:betadex