核磁共振光谱法用于表征地塞米松磷酸钠与环糊精在溶液中的包合物结构以及分析潜在竞争效应的效用。

Utility of nuclear magnetic resonance spectroscopy to characterize the structure of dexamethasone sodium phosphate inclusion complexes with cyclodextrins in solution and to analyze potential competitive effects.

作者信息

Echezarreta-López M M, Perdomo-López I, Estrada E, Vila-Jato J L, Torres-Labandeira J J

机构信息

Departamento de Farmacia e Tecnoloxía Farmacéutica, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Universitario Sur, E-15782 Santiago de Compostela, Spain.

出版信息

J Pharm Sci. 2002 Jun;91(6):1536-47. doi: 10.1002/jps.10145.

DOI:10.1002/jps.10145

PMID:12115852

Abstract

The interaction between dexamethasone sodium phosphate (DSP) and four cyclodextrin (CyD) derivatives [2,6-di-O-beta-cyclodextrin (DIMEB), gamma-cyclodextrin (gamma-CyD), and hydroxypropyl-beta-cyclodextrin with either 2.7 or 4.6 degrees of substitution (HPbetaCyD 2.7 and HPbetaCyD 4.6, respectively)] was investigated by proton nuclear magnetic resonance spectroscopy (1H NMR). The data suggested the formation of inclusion complexes in solution in which B and C rings of the molecule are located inside the cavity. Nevertheless, the structure, in terms of depth within CyD, depends on the derivative considered. Molecular mechanics calculations of DSP complexes with DIMEB and gamma-CyD support the NMR results. The potential displacement of DSP from the CyD cavity by usual ophthalmic drugs (e.g., polymyxin B, trimethoprim, and benzalkonium chloride) was determined by NMR. The technique has been found useful to analyze this problem in pharmaceutical preparations.

摘要

通过质子核磁共振光谱法（1H NMR）研究了地塞米松磷酸钠（DSP）与四种环糊精（CyD）衍生物[2,6-二-O-β-环糊精（DIMEB）、γ-环糊精（γ-CyD）以及取代度分别为2.7或4.6的羟丙基-β-环糊精（分别为HPβCyD 2.7和HPβCyD 4.6）]之间的相互作用。数据表明在溶液中形成了包合物，其中分子的B环和C环位于腔内。然而，就CyD内部的深度而言，其结构取决于所考虑的衍生物。DSP与DIMEB和γ-CyD复合物的分子力学计算支持了核磁共振结果。通过核磁共振确定了常用眼科药物（如多粘菌素B、甲氧苄啶和苯扎氯铵）从CyD腔中置换DSP的可能性。已发现该技术对于分析药物制剂中的这一问题很有用。