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

将开发新的加工方法来解决许多药品的一个主要技术问题，即稳定性问题。处于分子无序或无定形状态的药物比处于分子有序或结晶状态的药物更有利，因为无定形物质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，非晶态药物通常不稳定，可以从非晶态结晶，尽管速度很慢。这项学术联络与工业（GOALI）合作研究项目的目的是获得对非晶态结晶的基本理解，并开发新的加工策略来制造稳定形式的非晶态药物。研究结果预计将促进新的非晶态药物配方的开发，从而使美国经济和社会受益。该项目的研究生将在涉及制造工程，非晶和晶体物理以及制药科学的多学科科学研究方面进行培训。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。与非晶态药物相关的基础知识将在这个项目中进行。玻璃态的结晶或反玻璃化将使用结晶材料的时间-温度转变图作为框架来解决。这项研究是基于这样一个假设：如果避免图中的成核鼻和结晶鼻，前者发生的时间更短，就可以制造出更稳定的非晶态药用玻璃。闪光扫描量热法将有助于探索大范围的非常高的冷却速率或短的等温结晶/成核时间，以便建立将特定化合物制成稳定玻璃的潜力界限。喷雾干燥、气相沉积和熔融挤压方法也将作为制造稳定的玻璃状药物的加工途径进行研究。玻璃态的结晶动力学将通过量热法进行研究，并将建立从介电光谱和粘弹性方法获得的与玻璃态动力学的关系。

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.