GOALI/Collaborative Research: Processing and Stability of Amorphous Dispersions for Advanced Pharmaceutical Applications

GOALI/合作研究：用于先进制药应用的无定形分散体的加工和稳定性

• 批准号: 1662039
• 负责人: Raj Suryanarayanan
• 金额: $ 19.97万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1662039&HistoricalAwards=false
• 关键词: GOALI; Collaborative; Research; Processing; Stability

New processing methods will be developed to combat a major technological problem of many pharmaceuticals, namely that of stability. Pharmaceuticals that are in the molecularly-disordered, or amorphous, state are advantageous compared to molecularly-ordered, or crystalline, forms of the same drug because the amorphous material has higher solubility in water and higher bioavailability. Consequently, lower doses can be used, decreasing both cost and the probability of toxic side effects. However, amorphous pharmaceuticals are generally not stable and can crystallize, albeit slowly, from the amorphous state. The aim of this Grant Opportunity for Academic Liaison with Industry (GOALI) collaborative research project is to gain a fundamental understanding of crystallization from the amorphous state and to develop new processing strategies to make stable forms of amorphous pharmaceuticals. The results are anticipated to facilitate development of new amorphous drug formulations and to, thus, benefit the U.S. economy and society. The graduate students on the project will be trained in this multidisciplinary scientific research that involves manufacturing engineering, amorphous and crystal physics, and pharmaceutical science. The collaboration with the industrial partner will ensure commercial consideration and provide a unique and broad-perspective training opportunity for the students. Fundamental knowledge related to amorphous pharmaceuticals will be pursued in this project. The crystallization or devitrification from the glassy state will be addressed using as a framework, the time-temperature-transformation diagram for crystallizing materials. The research is based on the hypothesis that one can create more stable amorphous pharmaceutical glasses if the nucleation nose of the diagram and the crystallization nose are both avoided, with the former occurring at shorter times. Flash scanning calorimetry will facilitate exploration of a wide range of very high cooling rates or short isothermal crystallization/nucleation times in order to establish the bounds of the potential for making specific compounds into stable glasses. Spray drying, vapor deposition, and melt extrusion methods will also be investigated as processing paths to create stable glassy pharmaceuticals. Crystallization kinetics from the glassy state will be studied by calorimetry, and the relationship to glassy dynamics, as obtained from dielectric spectroscopy and viscoelastic methods, will be established.

将开发新的加工方法，以解决许多药品的一个主要技术问题，即稳定性问题。与分子有序或结晶形式的同一药物相比，处于分子无序或无定形状态的药物具有优势，因为无定形材料在水中具有更高的溶解度和更高的生物利用度。因此，可以使用较低的剂量，从而降低成本和毒副作用的可能性。然而，无定形药物通常不稳定，可以从无定形状态结晶，尽管速度很慢。GOALI合作研究项目的目的是对非晶态结晶有一个基本的了解，并开发新的加工策略来制造稳定形式的非晶态药物。预计这一结果将促进新的无定形药物配方的开发，从而使美国经济和社会受益。该项目的研究生将接受这一涉及制造工程、非晶态和晶体物理以及制药科学的多学科科学研究的培训。与行业合作伙伴的合作将确保商业考虑，并为学生提供独特和广阔的培训机会。本项目将学习与无定形药物有关的基础知识。玻璃态的结晶或析晶将以结晶材料的时间-温度-转变图为框架来处理。这项研究是基于这样一个假设，即如果图中的成核鼻子和晶化鼻子都被避免，那么人们可以产生更稳定的非晶态药物玻璃，前者发生的时间更短。闪光扫描量热法将有助于探索广泛的极高冷却速度或短等温结晶/成核时间，以便确定将特定化合物制成稳定玻璃的可能性范围。还将研究喷雾干燥、气相沉积和熔融挤出方法，作为生产稳定玻璃药物的加工途径。从玻璃态的结晶动力学将用量热法研究，并将建立与玻璃动力学的关系，如介电光谱和粘弹性方法所获得的。

项目成果

Effect of glycerol on the order of the mesophase transitions of supercooled itraconazole

甘油对过冷伊曲康唑中间相转变顺序的影响

• DOI: 10.1016/j.molliq.2020.114222
• 发表时间: 2020
• 期刊: Journal of Molecular Liquids
• 影响因子: 6
• 作者: Amponsah-Efah, Kweku K.;Glorieux, Christ;Thoen, Jan;Suryanarayanan, Raj
• 通讯作者: Suryanarayanan, Raj