Waleczek K J, Marques H M Cabral, Hempel B, Schmidt P C
Department of Pharmaceutical Technology, Eberhard-Karls-University Tuebingen, Tuebingen, Germany.
Eur J Pharm Biopharm. 2003 Mar;55(2):247-51. doi: 10.1016/s0939-6411(02)00166-2.
(-)-Alpha-bisabolol was found to form an inclusion complex with beta-cyclodextrin (beta-CD) in solution as well as in the solid state. To investigate molecular associations of beta-CD with pure (-)-alpha-bisabolol or (-)-alpha-bisabolol as a component of camomile essential oil, phase solubility studies were undertaken. A B(s) type solubility with an apparent complex constant of 273 M(-1) for the pure (-)-alpha-bisabolol and 304 M(-1) for (-)-alpha-bisabolol as a constituent of the essential oil were obtained. The two curves in the phase solubility diagram reach their plateau at different concentrations of (-)-alpha-bisabolol, 7.04 x 10(-4) M for the pure substance and 2.88 x 10(-4) M for the substance as a component of the essential oil. Although the shapes of the curves are almost similar, the intrinsic solubility's of pure (-)-alpha-bisabolol (4.85 x 10(-4) M) and (-)-alpha-bisabolol as a component of the essential oil (1.82 x 10(-4) M) differ significantly. An inclusion complex having a stoichiometric composition of 2:1 (beta-CD: drug) was obtained. A mechanism of complexation has been proposed on the basis of the stability constant calculated from phase solubility data and the stoichiometric ratio of the solid state complexation.
研究发现,(-)-α-红没药醇在溶液和固态下均能与β-环糊精(β-CD)形成包合物。为了研究β-CD与纯(-)-α-红没药醇或作为洋甘菊精油成分之一的(-)-α-红没药醇之间的分子缔合,进行了相溶解度研究。对于纯(-)-α-红没药醇,获得了表观络合常数为273 M⁻¹的B(s)型溶解度曲线;对于作为精油成分的(-)-α-红没药醇,表观络合常数为304 M⁻¹。相溶解度图中的两条曲线在不同浓度的(-)-α-红没药醇处达到平台期,纯物质为7.04×10⁻⁴ M,作为精油成分的物质为2.88×10⁻⁴ M。尽管曲线形状几乎相似,但纯(-)-α-红没药醇(4.85×10⁻⁴ M)和作为精油成分的(-)-α-红没药醇(1.82×10⁻⁴ M)的固有溶解度存在显著差异。得到了化学计量比为2:1(β-CD:药物)的包合物。基于从相溶解度数据计算得到的稳定常数和固态络合的化学计量比,提出了一种络合机制。