Our group focuses on crystal engineering and crystallization process development. By understanding and modifying solid state properties we also aim at developing novel crystallization applications. We strive to understand crystallization processes that are still at early stage of development (R&D, gram to kilogram scale), as well as processes that are being brought up to industrial scale (from early-scale up, through pilot-plant, and up to production scale).
Crystal Engineering
In crystal engineering, one aims at fine-tuning the properties of the solid state, by using knowledge on intermolecular interactions responsible for a given crystal lattice.
We work in this field on thermo- , photochromic and solvatochromic compounds , which are materials that change color upon heating, irradiation or solvatation. By alterning the nature of the solid state we aim at impacting these properties.
Photo- and thermochromism
Chromotropism is a reversible color change linked to structural (or environmental changes). A lot of attention has been paid to those compounds that change color due to external stimuli such as temperature (thermochromism), irradiation (photochromism) or solvent exchange (solvatochromism). Most compounds are responsive in solution, as the response often implies strong structural changes. We try to render compounds chromotropic at the solid state, by altering the nature of the solid state.
Amongst others we work on anils, which are known to be thermo- as well as photochromic.
Control of powder quality
Final powder of a pharmaceutically active compound can present unwanted properties (flowability, hygroscopicity, particle size, ...). We aim at controlling these properties by crystal engineering. In this context, we tackled the hygroscopicity of lactic acid through co-crystallization. Lactic acid can be co-crystallized with D-tryptophane removing its deliquescence.
Crystallization process development
Crystallizations are often the final step in the production of organic or inorganic compounds. This step is therefore directly determinant for the final outcome (yield, purity, etc.). Although these processes seem quite straightforward, problems such as caking, yield loss, unexpected polymorphism, un-controlled particle size distribution,... frequently occur, even on industrial scale. These problems can most of the time be avoided by a more profound understanding of the crystallization process. During process development, often less than 10% of the total effort is dedicated to crystallization development, which seems contradictory to the evident importance of this step. A small overview of recent litterature will show the interested reader that crystallization is still `poorly` understood from a fundamental point of view. However some common rules should always be followed when developping a crystallization process.
- Study the solid state of the compound (polymorphism, solvatism, racemic/conglomerate compound, solid liquid phase diagrams, ....)
- Introduce a solvent into the picture (solvent screening, solubility diagrams, ternary phase diagrams, ...)
- Study process parameters at a lower scale (stirrer type and rate, reactor design, seeding, particle size, ...)
- Scale-up the process
Although interested in all four areas, our current focus lies in the development of alternative solid forms and the use hereof to stabilize the system (control of solid state), to develop new applications, or even to use as alternative new formulation form of pharmaceutical compounds. We are currently active in the field of resolution, purification, separation through formation of multi-component crystals. We also investigate controlling the properties of the final solid form to avoid process issues (eg. hygroscopicity, stability, ...)
As part of our research we focus on developing and upscaling crystallization processes for pharmaceutically active as well as food compounds. We do this for industrial as well as academic partners, working on drugs in development, as well as drugs/food compounds which are already marketed but which require an optimized process.
Co-crystal screening
Our laboratory has a particular expertise in co-crystal screening. We are continuously on the look-out to improve co-crystal screening methods, and work on a multitude of active pharmaceutical ingredients. In this context, we identified novel co-crystals of Levetiracetam, using Piracetam as a template, and achieving a high co-crystal succesrate.
Co-crystallization from solution
We also combine our expertise in co-crystal screening with that of the crystallization process, focusing on developing co-crystallization processes from solution. In this context, we have extended expertise in development of ideal process conditions and construction of co-crystal phase diagrams.
Novel solution based co-crystal applications
We also try to go beyond mere co-crystallization from solution, by looking into novel co-crystallization applications.
In this context, we showed how, unlike salts, co-crystals behave enantiospecifically, and used this peculiarity to develop a novel resolution process, for those compounds that do not or not easily form salts. Once more, we developed an expertise in solution thermodynamics. As an example we resolved Levetiracetam from a racemic mixture, using S-mandelic acid as a chiral resolution agent.
