Industry/University Cooperative Research: Microspherical Polymer Matrix Formation by Rapid Expansion of SupercriticalSolutions (RESS) and Mathematical Modelling of RESS.

产学合作研究：通过超临界溶液（RESS）快速膨胀形成微球聚合物基质以及RESS的数学建模。

• 批准号: 9000614
• 负责人: Pablo Debenedetti
• 金额: $ 17.15万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9000614&HistoricalAwards=false
• 关键词: Industry; University; Cooperative; Research; Microspherical

This project is an investigation of the rapid expansion of supercritical solutions (RESS) as a means of producing monodisperse polymer microspheres and of incorporating low molecular weight compounds into the polymer matrix. Polymers studied include polylactic and polyglycolic acids and their copolymers, polystyrene, and polymethacrylates. Low molecular weight co-precipitates studied include the model compounds naphthalene and phenanthrene, as well as progesterone, a contraceptive steroid. The mathematical modeling of the RESS process constitutes the theoretical component of this project. The goal is to understand quantitatively how process variables influence the size distribution of RESS powders. Precipitation in RESS occurs as a result of a sudden expansion which propagates at the speed of sound. This leads to essentially uniform supersaturation in the nucleating medium, giving rise to particles with narrow size distributions. The nonideality of supercritical solutions gives rise to exceptionally high supersaturation ratios upon expansion, and hence to very small particles. To date, the idea of applying this novel process to the production of polymer microspheres for sustained drug release, combining into one step particle production, low molecular weight drug incorporation and size reduction has not been explored. No quantitative treatment of the RESS process exists to date. The proposed model accounts for nonidealities peculiar to supercritical mixtures, such as endothermic solute condensation, and high solvent compressibility. Polymer microspheres are used as chromatography packings, calibration standards, and sustained drug delivery devices. Problems associated with current methods for the production of polymeric microsphere powders include the need for solvent and surfactant elimination, poor control of particle size distribution, and, for drug delivery applications, the difficulty of incorporating drugs into the carrier particles uniformly and at high concentration. For micron or sub-micron particles, which can be made monodisperse but are colloidally stable, purification and drying are especially difficult steps. The RESS process has the potential for unifying particle production, incorporation of low molecular weight drugs, purification, and size reduction in a single step leading to solvent-free microspheres with a narrow size distribution. The resulting reduction in sample loss and contamination is especially important in drug delivery applications.

这个项目是一个快速扩张的调查， 超临界溶液（RESS）作为生产 单分散聚合物微球和掺入低 分子量化合物进入聚合物基质。 聚合物 所研究的包括聚乳酸和聚乙醇酸及其 共聚物、聚苯乙烯和聚甲基丙烯酸酯。 低分子 所研究的重量共沉淀物包括模型化合物 萘和菲，以及孕酮， 避孕类固醇 RESS的数学模型 这一过程构成了本项目的理论组成部分。 目标是定量地了解过程变量 影响RESS粉末的粒度分布。 RESS中的降水是突然膨胀的结果 它以音速传播 这导致 成核介质中基本上均匀的过饱和， 产生具有窄尺寸分布的颗粒。 的 超临界溶液的非理想性引起 膨胀时异常高的过饱和比，以及 因此是非常小的颗粒。 到目前为止， 该新方法用于生产聚合物微球， 为了持续药物释放，组合成一步颗粒 生产、低分子量药物掺入和尺寸 还没有探索减少。 没有定量治疗 RESS进程至今仍存在。 拟议的模式账户 对于超临界混合物特有的非理想性，例如 吸热溶质缩合和高溶剂 压缩性 聚合物微球用作色谱填料， 校准标准和持续给药装置。 与目前生产聚乙烯醇的方法有关的问题 聚合物微球粉末包括对溶剂的需要， 表面活性剂消除，粒度控制不良 分配，并且对于药物递送应用， 将药物结合到载体颗粒中的困难 均匀且高浓度。 对于微米或亚微米 颗粒，其可以被制成单分散的，但是是胶体的， 稳定、纯化和干燥特别困难 步 RESS过程有可能统一粒子 生产，掺入低分子量药物， 纯化和尺寸减小在一个步骤中， 无溶剂的微球具有窄的尺寸分布。 样品损失和污染的减少是 在药物递送应用中尤其重要。