Determination of stability constant of beta-cyclodextrin complexes using the membrane permeation technique and the permeation behavior of drug-competing agent-beta-cyclodextrin ternary systems.
The stability constants (Kc) of beta-cyclodextrin (beta-CyD) complexes with phenacetin and various benzoic acids were determined using the membrane permeation technique using a cellophane membrane permeable for guest molecules which was impermeable for beta-CyD molecules. The permeation rate equations of guests in the presence of beta-CyD in the donor phase were derived and the permeation profiles were analyzed as a function of time to determine the Kc values. The Kc values determined using the membrane permeation technique were in close agreement with those determined by the conventional kinetic method and the solubility method. The membrane permeation technique is of greater advantage than the conventional methods, because in the former method the stability constant can be obtained from only one experimental run by analyzing the permeation data as a function of time. In the latter method, on the other hand, some property changes have to be measured at various CyD concentrations and in turn analyzed as a function of CyD concentration. The permeation profiles of phenacetin of the drug-competing agent-beta-CyD ternary system were estimated by using the stability constants and the experimental curves closely matched the theoretically derived ones.
Ono
N
N
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Hirayama
F
F
Arima
H
H
Uekama
K
K
D000465:Algorithms; D001565:Benzoates / Q000737:chemistry; D002476:Cellophane; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D010539:Permeability; D010615:Phenacetin / Q000737:chemistry; D012995:Solubility; D047392:beta-Cyclodextrins
D001565:Benzoates; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D002476:Cellophane; D010615:Phenacetin; C031215:betadex