ERI: Solubility-Boosting Effect of Lattice Impurities in Anisotropic Crystals

ERI：各向异性晶体中晶格杂质的增溶作用

• 批准号: 2301629
• 负责人: Gerard Capellades Mendez
• 金额: $ 19.99万
• 依托单位: Rowan University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2301629&HistoricalAwards=false
• 关键词: ERI; Solubility; Boosting; Effect; Lattice

Understanding particle solubility is critical for the design of industrial crystallizers, semiconductor manufacturing operations, and separation processes such as reverse osmosis desalination, where unwanted scaling is an operational challenge. It is an important design consideration in the synthesis of pharmaceuticals where control of solubility is required for optimal drug delivery. The lack of solubility control also can be a limiting factor in the formulation of food products and diet supplements. Past studies of the solubility of crystalline materials have focused on the effects of crystal lattice structure and liquid composition on solubility. These studies have largely ignored the role composition variations within individual crystals play in solubility, likely due to the difficulty of measuring these variations. This project will investigate whether compositional variations within a crystal can result in different solubilities among the crystal facets, resulting in uneven growth or dissolution within individual crystals. The research will challenge current models of crystal growth and dissolution processes and will produce new insights into how impurities are released from crystalline materials, creating new routes to extracting potentially toxic impurities from pharmaceutical products. The project will contribute to the education of ten to twenty undergraduate students and one Ph.D. student, who will gain hands-on experience with crystallization processes and analysis of crystalline materials, a skillset valued in the pharmaceutical industry but rarely found in graduates joining the U.S. workforce.This project presents a new approach to studying the effect of lattice-incorporated impurities on crystal solubility. The proposal is based on the premise that crystals can exhibit differing degrees of composition anisotropy, with certain regions being entirely responsible for hosting impurities. This motivates the research plan to investigate the effect that lattice impurities have on crystal form stability and solubility, that these properties should be studied with respect to individual crystal facets and not on powders (of crystals) as a whole. This project sets out to prove the hypothesis that a single crystal may present multiple solubility values across its lattice, and that those differences can be leveraged in the design of novel impurity separation strategies. This research project is divided in two research aims. In Aim 1, research will concentrate on characterizing anisotropy of impurities within single crystals and investigating how impurity gradients affect dissolution and growth. Aim 2 will then expand to the study of crystal suspension aging dynamics by investigating how coexisting pure and impure lattices affect the dissolution and growth behaviors during suspension aging. The research will make use of model anisotropic systems with transparent solutes and opaque impurities, where the presence and extent of anisotropy can be easily studied. The proposed research is integrated with an education plan that will provide undergraduate and graduate students with specialized skills in separation processes and materials science, as well as with experience working in multidisciplinary teams. The undergraduate students will be divided into two groups, aligned with the two Aims of the research proposal, resulting in an effective mechanism for integrating the PI’s research and education efforts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

了解颗粒溶解度对于工业结晶器、半导体制造操作和反渗透海水淡化等分离过程的设计至关重要，在这些过程中，不需要的结垢是一个操作挑战。这是药物合成中的一个重要设计考虑因素，其中需要控制溶解度以实现最佳药物输送。 缺乏溶解度控制也可能是食品和膳食补充剂配方中的限制因素。过去对晶体材料溶解度的研究主要集中在晶格结构和液体组成对溶解度的影响。这些研究在很大程度上忽略了单个晶体内的组成变化在溶解度中所起的作用，可能是由于测量这些变化的困难。该项目将研究晶体内的成分变化是否会导致晶面之间的溶解度不同，从而导致单个晶体内生长或溶解不均匀。该研究将挑战当前的晶体生长和溶解过程模型，并将对杂质如何从晶体材料中释放产生新的见解，从而创建从药品中提取潜在有毒杂质的新途径。该项目将有助于培养十到二十名本科生和一名博士生。学生将获得结晶过程和晶体材料分析的实践经验，这是制药行业重视的技能，但在加入美国劳动力市场的毕业生中很少见。该项目提出了一种研究晶格掺入杂质对晶体溶解度影响的新方法。该提议基于这样的前提：晶体可以表现出不同程度的成分各向异性，其中某些区域完全负责容纳杂质。这促使研究计划调查晶格杂质对晶型稳定性和溶解度的影响，这些特性应该针对单个晶面而不是整个粉末（晶体）进行研究。该项目旨在证明单晶可能在其晶格中呈现多个溶解度值的假设，并且可以在设计新颖的杂质分离策略时利用这些差异。该研究项目分为两个研究目标。在目标 1 中，研究将集中于表征单晶内杂质的各向异性，并研究杂质梯度如何影响溶解和生长。然后，目标 2 将通过研究共存的纯晶格和不纯晶格如何影响悬浮液老化过程中的溶解和生长行为，扩展到晶体悬浮液老化动力学的研究。该研究将利用具有透明溶质和不透明杂质的各向异性模型系统，可以轻松研究各向异性的存在和程度。拟议的研究与一项教育计划相结合，该计划将为本科生和研究生提供分离过程和材料科学方面的专业技能，以及在多学科团队中工作的经验。本科生将被分为两组，与研究计划的两个目标保持一致，从而形成整合 PI 的研究和教育工作的有效机制。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。