Crystallization of Active Pharmaceutical Ingrediants

提案编号：CBET- 0651711首席研究员：Michael DohertyAFFILIATION：加州大学圣巴巴拉分校提案标题：活性药物成分的结晶拟议研究的目标是开发新一代的建模工具，由实验支持，用于有机晶体的生长和溶解，特别是活性药物成分（API）。新一代的模型将允许定量预测从溶液中生长的有机晶体的形状和溶液介导的多态性。具体任务包括开发晶面的基本生长和溶解模型，该模型考虑了复杂键链（由原料药分子的大小和结构引起）和溶剂对晶面生长/溶解速率的影响。提出了结晶实验来验证该方法的关键预测方面。模型系统将包括扑热息痛（对乙酰氨基酚），洛伐他汀（一种降胆固醇药物），以及从水和有机溶剂中生长的氨基酸。本研究项目的智力优势和主要贡献将是提供晶体化学和晶体工程之间的强耦合，以改进产品和工艺设计。主要的好处将是更可靠，高保真，预测模型，这将减少研究和开发时间的结晶产品和工艺技术。拟议的研究计划旨在开发定量的、可预测的工程设计模型，利用大量关于晶体的描述性文献信息，从而设计出改进的工程系统。这项工作的更广泛的影响将是表明固态化学可以与工程原理相结合。成功将对化学工程教育产生影响，通过潜在的新课程设置和教科书。它还将对工业研发工作实践产生影响。研究生研究助理将在这一重要领域接受教育，他们将帮助将技术转化为工业。

PROPOSAL NUMBER: CBET- 0651711PRINCIPAL INVESTIGATOR: Michael DohertyAFFILIATION: University of California Santa BarbaraPROPOSAL TITLE: Crystallization of Active Pharmaceutical IngredientsThe goal of the proposed research is to develop a new generation of modelingtools, supported by experiments, for the growth and dissolution of organic crystals,especially active pharmaceutical ingredients (API's). The new generation of modelswill allow quantitative predictions to be made for the shape of organic crystalsgrown from solution and for solution mediated polymorphism. The specific tasksinclude the development of fundamental growth and dissolution models for crystal faces that account for the influence of complex bond chains (caused by the size and structure of API molecules) and solvent on the face growth/dissolution rates. Crystallization experiments are proposed to validate the key predictive aspects of the approach. Model systems will include paracetamol (acetaminophen), Lovastatin (a cholesterol lowering drug), and amino acids grown from aqueous and organic solvents. The intellectual merit, and main contribution of this research program will be to provide a strong coupling between crystal chemistry and crystal engineering for improved product and process design. The major benefit will be more reliable, high fidelity, predictive models that will reduce research and development times for crystallization product and process technology. The proposed research program is geared towards the development of quantitative, predictive, engineering design models that harness the vast amounts of descriptive literature information about crystals so that improved engineering systems can be designed. The broader impact of this work will be to show that solid state chemistry can be coupled with engineering principles. Success will have an impact on chemical engineering education through the potential for new course offerings and textbooks. It will also have an impact on industrial R&D work practices. Graduate research assistants will be educated in this important area, and they will help to transfer the technology to industry.