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首页> 外文学位 >Solid-state NMR analysis of excipients and drug-excipient interactions in the amorphous state.
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Solid-state NMR analysis of excipients and drug-excipient interactions in the amorphous state.

机译：非晶态状态下赋形剂和药物-赋形剂相互作用的固态NMR分析。

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摘要

Solid-state NMR (SSNMR) experiments were used to investigate numerous aspects of pharmaceutically relevant amorphous materials, such as structure, molecular weight, water content, interactions with other molecules, and molecular mobility. This dissertation highlights the benefit of using SSNMR in conjunction with other techniques to gain a fuller understanding of the solid-state properties of amorphous pharmaceutical samples.The application of SSNMR to the analysis of polysaccharide-based excipients was demonstrated. Excipients that were studied included the following: alginic acid and sodium alginate, carrageenans, starch and derivatives, microcrystalline cellulose, and cellulose-based derivatives such as hydroxyethylcellulose, (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC). Results showed that although the peaks in the SSNMR spectra of these samples were broad, the resolution was sufficient for accurate form identification and differentiation. Relaxation measurements provided unique information on starch derivatives. A linear correlation between T1, the peak area of new signals, and the extent of hydrolysis of starch derivatives was observed.Experiments to explore the potential for SSNMR parameters to be correlated to functionally related characteristics of sodium alginate were performed. The ability to detect variations in monomer content among different grades was demonstrated. Hydration was found to increase the resolution of signals in the SSNMR spectra. Differences in intrinsic viscosity and molecular weight of samples with similar monomer content were correlated to SSNMR relaxation times.The hydrogen-bonding networks of the crystalline forms and the melt-quenched amorphous form of indomethacin were analyzed using SSNMR. Disruptions of this network when intimately mixed with PVP or HPMC were detected. SSNMR data supported the conclusion that indomethacin forms hydrogen bonds with PVP and HPMC at the expense of forming hydrogen bonds with other indomethacin molecules.The miscibility and mobility of indomethacin amorphous solid dispersions was probed using SSNMR relaxation measurements. Based on relaxation values, indomethacin appeared to form a miscible amorphous solid dispersion with HPMC at all conditions studied and with PVP in solvent-evaporated mixtures. Melt-quenched indomethacin:PVP mixtures appeared only partially miscible by SSNMR relaxation measurements, suggesting that better mixing was achieved using solvent evaporation. The mobility of amorphous indomethacin was significantly reduced in the presence of both PVP and HPMC.
机译：固态NMR（SSNMR）实验用于研究药学上相关的无定形物质的许多方面，例如结构，分子量，水含量，与其他分子的相互作用以及分子迁移率。这篇论文强调了将SSNMR与其他技术结合使用的好处，可以更全面地了解无定形药物样品的固态特性。证明了SSNMR在多糖类赋形剂分析中的应用。研究的赋形剂包括：藻酸和藻酸钠，角叉菜胶，淀粉及其衍生物，微晶纤维素以及基于纤维素的衍生物，例如羟乙基纤维素（HEC），羟丙基纤维素（HPC）和羟丙基甲基纤维素（HPMC）。结果表明，尽管这些样品的SSNMR谱图中的峰宽，但分辨率足以进行准确的形式鉴定和区分。弛豫测量提供了有关淀粉衍生物的独特信息。观察到T1，新信号的峰面积和淀粉衍生物的水解程度之间存在线性关系。进行了探索SSNMR参数与藻酸钠功能相关特性相关的潜力的实验。证明了检测不同等级之间单体含量变化的能力。发现水合增加了SSNMR谱中信号的分辨率。单体含量相近的样品的特性粘度和分子量差异与SSNMR弛豫时间有关。吲哚美辛的结晶形式和熔融淬灭无定形形式的氢键网络均采用SSNMR分析。当与PVP或HPMC紧密混合时，会检测到该网络中断。 SSNMR数据支持了吲哚美辛与PVP和HPMC形成氢键，但与其他吲哚美辛分子形成氢键的结论。使用SSNMR弛豫测量法研究了吲哚美辛无定形固体分散体的混溶性和迁移性。基于弛豫值，吲哚美辛似乎在所有研究的条件下均与HPMC和与PVP在溶剂蒸发的混合物中形成可混溶的无定形固体分散体。通过SSNMR弛豫测量，熔融淬灭的消炎痛：PVP混合物似乎仅部分混溶，表明使用溶剂蒸发可实现更好的混合。在PVP和HPMC的存在下，非晶吲哚美辛的迁移率显着降低。

著录项

  • 作者

    Sperger, Diana M.;

  • 作者单位

    University of Kansas.;

  • 授予单位 University of Kansas.;
  • 学科 Chemistry Pharmaceutical.Chemistry Physical.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 259 p.
  • 总页数 259
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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