Scientific context

Drug development often faces a critical trade-off between stability and bioavailability. Given that poor solubility frequently limits therapeutic efficacy, optimizing the physical state of a drug remains a cornerstone challenge in pharmaceutical engineering. Polymorphism—the ability of an Active Pharmaceutical Ingredient (API) to exist in multiple crystalline forms without altering its chemical identity—offers a powerful solution. Distinct polymorphs can lead to vastly different physicochemical properties, including solubility, dissolution rates, stability, and ultimately, clinical performance.

While high-pressure techniques are widely used in materials science to engineer new phases, they hold untapped potential for therapeutic molecular solids. These materials are highly sensitive to environmental stressors, particularly pressure, due to the weak intermolecular interactions governing their crystal lattices. By leveraging high-pressure synthesis, we can perturb these interactions to access novel metastable polymorphic forms, opening new pathways for the design of optimized, high-performance pharmaceuticals. The PhD proposal combines advanced experimental techniques with atomistic simulations to overcome current limitations in drug solubility and bioavailability.

What will we do?

Experiments: The laboratory's experimental facilities will be used to explore the pressure-temperature diagrams of selected active ingredients and stabilize new polymorphic forms. Simultaneously, Raman spectroscopy and X-ray diffraction (XRD) will provide structural information to obtain precise quantification and spatial mapping of the resulting polymorphs. To confirm the structural characterization of new pressure-induced phases, we will also perform synchrotron experiments.
Simulation: By integrating AI-assisted simulations with rare-event sampling, we will study phase transitions in molecular solids. Machine-learning potentials will provide DFT-level accuracy at reduced costs, while enhanced sampling will elucidate nucleation mechanisms and quantify nucleation rates across a broad P−T landscape. Ultimately, these models will map phase behavior to directly predict and guide experimental outcomes.

What do we oﬀer?

A highly interdisciplinary problem: Develop a versatile research profile combining physics, chemistry and pharmaceutical science with the possibility to learn many key research skills including high-pressure experiments, Raman spectroscopy, X-ray diffraction, HPC computing, machine-learning assisted simulations, rare-event sampling and big data analysis.

High-Impact Mentorship in a Human-Sized Team: Join an agile, close-knit research group where you will benefit from direct mentorship of two complementary PIs with dedicated support for learning both experimental and computational skills and opportunities to co-supervise Master’s students.

Lille, a Strategic Research Hub: Thrive in an affordable, bike-friendly city. Enjoy a high quality of life while being located at the crossroads of Europe just one hour from Paris, London, and Brussels.

French Work-life Balance: Beyond a competitive salary, you’ll receive world-class healthcare, generous paid leave, and a robust social safety net designed to support your long-term career transitions.

How to apply?

Send an email to [email protected] and [email protected] with your CV , your academic record and a cover letter specifically stating why you are interested in this position and what you can bring to the table.

[PhD] High-Pressure Synthesis of Optimized APIs: Experimental and Computational Studies