Wulff Marie, Aldén Maggie, Tegenfeldt Jörgen
Department of Physical and Inorganic Pharmaceutical Chemistry, Box 580, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden.
Bioconjug Chem. 2002 Mar-Apr;13(2):240-8. doi: 10.1021/bc000156o.
Various solid dispersions of alpha-, beta- and gamma-cyclodextrin (CD) in PEG 6000 with and without the addition of 5% w/w indomethacin were prepared by the melting method using the original components. The samples were investigated by solid-state (13)C NMR, and the interactions between the drug and the cyclodextrins were evaluated. The indomethacin-gamma-CD phase with tetragonal symmetry found in a previous X-ray study gave chemical shifts which suggested that this phase is a complex between indomethacin and gamma-CD. Evidence of an indomethacin-beta-CD complex were found. A distribution of the chemical shifts for beta-CD was attributed to the possible formation of different types of complexes between indomethacin and beta-CD. No complex formation was found in the alpha-CD system. The degree of relative crystallinity of the samples in the gamma-CD system was measured by (1)H NMR, X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and modulated-temperature DSC (MTDSC). The results obtained by the NMR, XRD, and DSC techniques showed that the dispersions were less crystalline than the pure polymer carrier, and the dispersion containing the indomethacin-gamma-CD complex had the lowest degree of crystallinity. By the MTDSC method a deviation was found for the PEG 6000/indomethacin dispersion. This emphasizes that the different techniques give specific information on the crystallinity.
采用原始组分通过熔融法制备了α-、β-和γ-环糊精（CD）在聚乙二醇6000中的各种固体分散体，其中一些添加了5% w/w的吲哚美辛，另一些未添加。通过固态（13）C核磁共振对样品进行了研究，并评估了药物与环糊精之间的相互作用。在先前的X射线研究中发现的具有四方对称性的吲哚美辛-γ-环糊精相给出的化学位移表明，该相是吲哚美辛与γ-环糊精之间的复合物。发现了吲哚美辛-β-环糊精复合物的证据。β-环糊精化学位移的分布归因于吲哚美辛与β-环糊精之间可能形成的不同类型的复合物。在α-环糊精体系中未发现复合物形成。通过（1）H核磁共振、X射线粉末衍射（XRD）、差示扫描量热法（DSC）和调制温度DSC（MTDSC）测量了γ-环糊精体系中样品的相对结晶度。核磁共振、XRD和DSC技术获得的结果表明，分散体的结晶度低于纯聚合物载体，且含有吲哚美辛-γ-环糊精复合物的分散体结晶度最低。通过MTDSC方法发现聚乙二醇6000/吲哚美辛分散体存在偏差。这强调了不同技术给出了关于结晶度的特定信息。
