Physicists Working at the Frontier of Materials and Pharmaceutical Science

Understanding Out of Equilibrium Systems with the CrystalBreeder



This work is provided by Jean-François Willart, a senior scientist at the French National Center for Scientific Research (CNRS). His research concerns the physical state of pharmaceutical materials with a special attention to the amorphous state.


The “Therapeutic and Molecular Materials” (MMT) team of the UMET laboratory at the University of Lille 1 is one of the very few groups of physicists working at the frontier of materials and pharmaceutical science. The research is dedicated to the physical state of pharmaceutical materials[1] with a special interest for glassy amorphous states[2]. Recently, a large part of our activities has concerned the optimization and the rationalization of drug/polymer systems. In particular, the team has developed a powerful experimental method to determine the state diagram of these systems[3] (i.e. solubility curves and glass transition curves). This method requires to anneal supersaturated mixtures at a given temperature to reach the equilibrium saturated state at this temperature by demixing and recrystallization of the excess drug. Depending on the temperature, the demixing process can be as long as several days.

Illustration of the two main solid state routes to reach the equilibrium saturated state of a drug () / polymer (▬) alloy: (1) Dissolution of the crystalline drug into the polymer; (2) Demixing and recrystallization of the drug from a supersaturated amorphous mixture. While the second one is noticeably faster, both processes are slow and require annealing for hours and even days to be completed.

We have found the CrystalBreeder to be a powerful tool to follow the evolutions of these out of equilibrium systems as it allows to perform, in parallel, long and accurate annealing of several samples at different temperatures. Moreover, it has been customized to accept several kinds of sample pans for calorimetry as well as Lindeman glass capillaries for powder X-ray diffraction, which are two analysis techniques commonly used in our lab. Samples can thus be analyzed immediately after annealing and then possibly replaced in the breeder to continue the annealing.


[1] M. Descamps and J.-F. Willart, in Disordered Pharmaceutical Materials (Wiley-VCH Verlag GmbH & Co. KGaA, 2016), p. 1.
[2] M. Descamps and J. F. Willart, Perspectives on the amorphisation/milling relationship in pharmaceutical materials, Advanced Drug Delivery Reviews 100, 51 (2016)
[3] A. Mahieu, J.-F. Willart, E. Dudognon, F. Danède, and M. Descamps, A New Protocol To Determine the Solubility of Drugs into Polymer Matrixes, Molecular Pharmaceutics 10, 560 (2013)