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Predictive Design of Polymer-Based Amorphous Solid Dispersion

聚合物基非晶固体分散体的预测设计

基本信息

批准号：
2030991
负责人：
金额：
--
依托单位：
University of Strathclyde
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2030991
关键词：
Predictive Design Polymer Based Amorphous

项目摘要

Amorphous solid dispersions comprising drug dissolved in polymers are known to enhance the dissolution performance and bioavailability of poorly water soluble drug. The exploitation of these approaches in marketed products has however been limited because of the inherent instability of the amorphous form, leading to physical instability and recrystallisation of the active ingredient rendering the product inactive. Thus, designing stable dispersed systems is a major challenge in the development of polymer based amorphous molecular dispersions. The aim of this project is to develop and test approaches for applying pair distribution function (PDF) analysis to reveal local short-range structure, and assess the ability to predict stable, metastable or unstable formulations. Specifically the project will develop tools that provide insight into structure-process-property interactions towards more predictive design of amorphous materials and formulated systems through control of short range packing within known solubility ranges. In addition, the project will provide experimental data to contribute to the development of advanced group contribution methods for drug-polymer solubility prediction. The aim of this project is to develop and test approaches for applying pair distribution function (PDF) analysis to reveal local short-range structure, and assess the ability to predict stable, metastable or unstable formulations. Specifically the project will develop tools that provide insight into structure-process-property interactions towards more predictive design of amorphous materials and formulated systems through control of short range packing within known solubility ranges. In addition, the project will provide experimental data to contribute to the development of advanced group contribution methods for drug-polymer solubility prediction. - The project will involve preparation of amorphous materials utilising melt-quench, lyophilisation and spray drying and exploit a suite of physical analysis methods in addition to x-ray scattering for PDF generation. - PDF analysis will be with combined with other techniques available in the CMAC National Facility including DSC, dissolution, nano-CT, imaging spectroscopies, AFM and ToF-SIMS to provide an unprecedented insight into the homogeneity, structure, physical composition and performance of molecular dispersions. Multivariate data analysis will be utilised to identify early changes in phase composition marking the onset of instability.- Solubility and phase composition data determined from these well characterised systems will then contribute directly to the development and testing of solubility predictions utilising the novel gSAFT framework being developed by collaborators at Imperial College (C. Adjiman).

已知包含溶解在聚合物中的药物的无定形固体分散体可增强水溶性差的药物的溶出性能和生物利用度。然而，由于无定形形式固有的不稳定性，这些方法在市售产品中的应用受到限制，导致活性成分的物理不稳定性和重结晶，从而导致产品失活。因此，设计稳定的分散体系是开发基于聚合物的无定形分子分散体的主要挑战。该项目的目的是开发和测试应用配对分布函数 (PDF) 分析来揭示局部短程结构的方法，并评估预测稳定、亚稳定或不稳定配方的能力。具体来说，该项目将开发工具，通过控制已知溶解度范围内的短程堆积，深入了解结构-过程-性能相互作用，从而对非晶材料和配方系统进行更具预测性的设计。此外，该项目还将提供实验数据，以促进药物-聚合物溶解度预测的先进基团贡献方法的开发。该项目的目的是开发和测试应用配对分布函数 (PDF) 分析来揭示局部短程结构的方法，并评估预测稳定、亚稳定或不稳定配方的能力。具体来说，该项目将开发工具，通过控制已知溶解度范围内的短程堆积，深入了解结构-过程-性能相互作用，从而对非晶材料和配方系统进行更具预测性的设计。此外，该项目还将提供实验数据，以促进药物-聚合物溶解度预测的先进基团贡献方法的开发。 - 该项目将涉及利用熔融淬火、冻干和喷雾干燥制备非晶材料，并利用除了 X 射线散射之外的一套物理分析方法来生成 PDF。 - PDF 分析将与 CMAC 国家设施中可用的其他技术相结合，包括 DSC、溶解、纳米 CT、成像光谱、AFM 和 ToF-SIMS，以提供对分子分散体的均匀性、结构、物理组成和性能的前所未有的洞察。多变量数据分析将用于识别标志着不稳定开始的相组成的早期变化。 - 从这些充分表征的系统中确定的溶解度和相组成数据将直接有助于利用帝国理工学院合作者（C. Adjiman）开发的新型 gSAFT 框架来开发和测试溶解度预测。