Research
Crystallization is a major issue in the development (purity, bioavailability ...), the production (feasibility, yield ...) and the industrial property (process patents, polymorphs ...) of fine chemicals. Efficient achieving of crystallization objectives requires specific knowledge, tools and skills.
Holodiag provides crystallization process development and optimization services. The Holodiag experts master
the fields of:
- Crystallization of small organic molecules (nucleation, growth ...)
- Thermoynamics of heterogeneous equilibria
- Phase diagrams
- Crystallography
- Molecular modelling
Holodiag owns a laboratory dedicated to crystallization and phase characterization. The analytical devices (c.f. Analytical services for further description) ensure an adapted answer to problematics regarding polymorphism (post-screening) and enantiopurification / optical resolution.
Polymorphism
The main solid states encountered are:Polymorphs : same composition but a different crystal packingHydrates/solvates (pseudo-polymorphs): a solvent is involved in the crystal packingSalts : salification of an acid or a base giving a different crystal packingAmorphous : non-crystalline solid exhibiting interesting bio-availability properties
The different possible solid states are highlighted by a preliminary screening step. However, the experimental crystallization conditions are not thoroughly investigated. Therefore, a post-screening step is needed to set up the parameters for the selective crystallization of a given solid state.
Holodiag provides R&D services for post-screening studies. Heterogeneous equilibria and phase diagrams (monotropy, enantiotropy, peritectic, non-congruent solubility ...) allow the determination of optimized crystallization conditions.
Enantiopurification / optical resolution
Access to pure enantiomers can be achieved by different methods. Crystallization is an efficient and cost-effective tool for the enrichment of mixtures or the enantiomeric resolution. Several routes can be contemplated:
Diastereomeric salts Preferential Crystallization Anti-conglomerate
Development and optimization are achieved by rationalization of the physico-chemical phenomena.
For the determination of the best crystallization conditions with respect to the customer needs (objectives)
only few tests are needed (no blind screening is performed to set up the conditions).
