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

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.