Effect of cyclodextrins on anthracycline stability in acidic aqueous media.
The effect of cyclodextrins on the stability of six anthracyclines in acidic medium at 50 degrees C has been investigated using a stability-indicating high pressure liquid chromatographic method. The influences of various parameters, such as the structure of cyclodextrins (alpha-cyclodextrin, beta-cyclodextrin, dimethyl-beta-cyclodextrin and gamma-cyclodextrin) and anthracyclines, cyclodextrin concentration, the pH and the presence of a co-solvent, are investigated. Lineweaver-Burk plots were used to calculate the stability constants of the various inclusion complexes as well as the rate constants for degradation of the anthracycline guest molecules in the complexes with the host cyclodextrins. Anthracyclines complexate only with gamma-cyclodextrin to a substantial extent. On complexation the stability of the guest molecule increases, however, the degradation pattern does not alter. The influence of the pH on the degradation of the included molecule is identical to that of the free drug. Addition of co-solvents, such as acetonitrile, causes decomposition of the complex.
Bekers
O
O
Department of Pharmaceutical Analysis, Faculty of Pharmacy, State University of Utrecht, the Netherlands.
Beijnen
J H
JH
Groot Bramel
E H
EH
Otagiri
M
M
Underberg
W J
WJ
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000494:pharmacology*; D003912:Dextrins / Q000494:pharmacology*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D012997:Solvents; D013053:Spectrophotometry; D013056:Spectrophotometry, Ultraviolet; D013213:Starch / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003505:Cyclodextrins; D003912:Dextrins; D012997:Solvents; D013213:Starch