Towards understanding milling induced disorder: Crystal defects formation and evolution in molecular crystals

Tao Feng, Purdue University

Abstract

Organic crystal structures are generally imperfect containing various types of crystal defects. These crystal defects interrupt the long-range three-dimensional order of the crystal lattice; these in turn are considered as disordered regions residing at higher levels in the energy landscape. Crystal defects may be formed when crystalline materials are subjected to milling process. Milling induced disorder has been very well studied in metals and inorganic materials; however, this type of study has rarely been conducted with pharmaceutical organic materials due to a lack of characterization methods that enable assessment and quantification of crystal defects. Little work has been done to differentiate the two types of disorder, amorphous vs crystal defects. The lack of understanding of the fundamental mechanism of milling induced disorder may cause significant uncertainty and unpredictability on materials’ properties during the development of drug products. Therefore, it is important to differentiate these two types of disorder and understand the impact of crystal defects on material properties and functionality. The present research focuses on the identification and characterization of crystal defects during the milling of organic molecular crystals. The crystal defects were differentiated from amorphous phase by thermal, diffraction, and spectroscopic methods. The formation and evolution of crystal defects were traced and characterized by various experimental techniques and computational methods. The pharmaceutical implications of crystal defects such as solubility and physical stability were also investigated. The effect of water was monitored on the defected crystal to determine any physical transformations.

Degree

Ph.D.

Advisors

Carvajal, Purdue University.

Subject Area

Pharmaceutical sciences|Materials science

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