Bekers O, Beijnen J H, Groot Bramel E H, Otagiri M, Underberg W J
Department of Pharmaceutical Analysis, Faculty of Pharmacy, State University of Utrecht, the Netherlands.
Pharm Weekbl Sci. 1988 Oct 14;10(5):207-12. doi: 10.1007/BF01956872.
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.
采用稳定性指示高效液相色谱法，研究了环糊精对六种蒽环类药物在50℃酸性介质中稳定性的影响。考察了各种参数的影响，如环糊精（α-环糊精、β-环糊精、二甲基-β-环糊精和γ-环糊精）和蒽环类药物的结构、环糊精浓度、pH值以及助溶剂的存在。利用Lineweaver-Burk图计算了各种包合物的稳定性常数以及蒽环类客体分子与主体环糊精形成的复合物中降解的速率常数。蒽环类药物仅与γ-环糊精大量络合。络合后客体分子的稳定性增加，但降解模式不变。pH值对被包合分子降解的影响与游离药物相同。添加助溶剂，如乙腈，会导致复合物分解。
