Shape Engineering of Organic Crystals

提案编号：CTS-0411630首席研究员：Michael Doherty机构：加州大学圣巴巴拉分校拟议研究的目标是开发新一代有机晶体生长和溶解的建模工具。该模型将允许定量预测溶液介导的多态性和从溶液中生长的有机晶体的颗粒大小和形状的同时预测。具体的任务包括一个动态模型的发展，以预测在生长和溶解过程中的晶体形状的演变，基本的生长和溶解模型的发展，占面生长/溶解速率的溶剂的影响，以及这些模型与人口平衡模型的整合，同时预测从溶液中生长的有机晶体的大小和形状。结晶器实验提出了验证的方法的关键预测方面。模型系统将包括从水和有机溶剂中生长的羧酸和氨基酸。 这项研究的一个方面将是提供晶体化学和结晶器工程设计之间的必要耦合。 这项工作的更广泛的影响将表明，固态化学可以与工程原理相结合。 该项目将通过新课程和教科书的潜力对化学工程教育产生影响。 这项工作可能会对制药行业产生重大影响，因为大多数产品都是以颗粒状结晶形式配制的。 评审员认识到这项工作的重要性和PI进行研究的能力。 PI具有集成固态化学、界面结构和建模算法的能力。 该研究将解决多态性的重要问题。 这将是具有挑战性的，因为多晶型对异质成核、溶剂、温度、过饱和和杂质敏感。 模型与实验室结晶器的连接是一个优点，将确保模型和实验之间的适当反馈。 该项目的成功完成将对晶体生长的方式产生广泛的影响。 它可以代表一个显着的进步，预测晶体形状的能力和添加剂和溶剂对形态的影响。

Proposal Number: CTS-0411630Principal Investigator: Michael DohertyInstitution: University of California-Santa BarbaraThe goal of the proposed research is to develop a new generation of modeling tools for the growth and dissolution of organic crystals. The models will allow quantitative predictions to be made for solution-mediated polymorphism and the simultaneous prediction of particle size and shape of organic crystals grown from solution. The specific tasks include the development of a dynamic model to predict the evolution of crystal shape during growth and dissolution, the development of fundamental growth and dissolution models for crystal faces that account for the influence of solvent on the face growth/dissolution rates, and the integration of these models with population balance models to simultaneously predict size and shape of organic crystals grown from solution. Crystallizer experiments are proposed to validate the key predictive aspects of the approach. Model systems will include carboxylic acids and amino acids grown from aqueous and organic solvents. One aspect of this research will be to provide the necessary coupling between crystal chemistry and crystallizer engineering design. The broader impact of this work will be to show that solid-state chemistry can be coupled with engineering principles. This project will have an impact on chemical engineering education through the potential for new course offerings and textbooks. This work could have a large impact on the pharmaceutical industry, where most products are formulated in particulate, crystalline form. Reviewers recognized the importance of the work and the ability of the PI to perform the research. The PI has the ability to integrate solid-state chemistry, interface structure, and modeling algorithms. The research will address the important problem of polymorphism. This will be challenging, as polymorphism is sensitive to heterogeneous nucleation, solvent, temperature, super saturation, and impurities. The connection of the modeling with a laboratory crystallizer is a plus and will ensure the proper feedback between modeling and experiment. Successful completion of the project would have broad impacts on the way crystal growth is viewed. It could represent a significant advance in the ability to predict crystal shape and the effects of additives and solvents on morphology.