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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

基本信息

批准号：
1662046
负责人：
Gregory McKenna
金额：
$ 25.37万
依托单位：
Texas Tech University
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 2020-11-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1662046&HistoricalAwards=false
关键词：
GOALI Collaborative Research Processing Stability

项目摘要

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，以解决许多药物的主要技术问题，即稳定性问题。处于分子无序或无定形状态的药物与相同药物的分子有序或结晶形式相比是有利的，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，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，并且可以从无定形状态结晶，尽管缓慢。这个学术联络与工业（GOALI）合作研究项目的目的是获得从无定形状态结晶的基本理解，并开发新的加工策略，使无定形药物的稳定形式。预计这些结果将促进新的无定形药物制剂的开发，从而使美国经济和社会受益。该项目的研究生将接受多学科科学研究的培训，涉及制造工程，非晶和晶体物理学以及制药科学。与工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。本项目将继续研究与无定形药物有关的基础知识。从玻璃态的结晶或失透将作为一个框架，结晶材料的时间-温度-转换图来解决。该研究是基于这样的假设，即如果避免图的成核鼻和结晶鼻，则可以创建更稳定的非晶药用玻璃，前者发生在更短的时间内。闪光扫描量热法将有助于探索宽范围的非常高的冷却速率或短的等温结晶/成核时间，以建立使特定化合物成为稳定玻璃的潜力的界限。喷雾干燥，气相沉积和熔融挤出方法也将被研究作为生产稳定的玻璃状药物的加工途径。从玻璃态的结晶动力学将通过量热法进行研究，并建立从介电谱和粘弹性方法获得的与玻璃态动力学的关系。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prediction of the Synergistic Glass Transition Temperature of Coamorphous Molecular Glasses Using Activity Coefficient Models

使用活性系数模型预测共晶分子玻璃的协同玻璃化转变温度

DOI：
10.1021/acs.molpharmaceut.1c00353
发表时间：
2021
期刊：
Molecular Pharmaceutics
影响因子：
4.9
作者：
Zhao, Xiao;Cheng, Sixue;Koh, Yung P.;Kelly, Brandon D.;McKenna, Gregory B.;Simon, Sindee L.
通讯作者：
Simon, Sindee L.

A calorimetry investigation of glass temperature and fragility of ancient ambers from Texas and Canada

对德克萨斯州和加拿大古代琥珀的玻璃温度和脆性进行量热研究