Improving the Crystal Morphology of Rufinamide by Experimental Structure Determination and Advanced Computational Approaches

Crystal shape and size are among the most important features of crystalline product that are prevalent in the pharmaceutical industry. Extremely fine and needle-like crystals pose various problems in the downstream processes including filtration, tableting, handling, and storage. Rufinamide is an anticonvulsant medication, and its most stable and therapeutically advantageous crystalline form shows notoriously undesirable morphology (filiform or thread-like) and is selected as a model compound for this study to change its morphology to a more equidimensional shape.

We approach this challenge by obtaining the atomic resolution of crystalline Rufinamide by single-crystal X-ray diffraction and identifying functional groups exposed on each crystalline surface. Using the obtained information from the crystal structure, we can use tailor-made additives to hinder the growth of the long axis and induce more equidimensional crystal formation. Computational approaches will also be performed on the obtained crystal structure, which provides a thermodynamic understanding of why needles are formed and how we can hinder their natural growth process by selected additives. The procedure developed in this research will provide valuable experimental data and theoretical understanding of controlling the morphology of pharmaceuticals.

Faculty Supervisor:

Sohrab Rohani

Student:

Partner:

University of Zurich

Discipline:

Engineering

Sector:

Pharmaceuticals; Other; Technology

University:

The University of Western Ontario

Program: