Strong knowledge in industrial manufacturing, thermodynamics of heterogeneous equilibria and phase diagrams allows us to identify critical parameters and optimize the process with effective robustness, scalability and reproducibility.
Crystallization can be seen as the last step of organic synthesis for product collection. Holodiag develops specific crystallization conditions after organic synthesis is completed. Starting material is the reaction medium.
Yield / purity optimization
Yield and purity never go up together. Typically, for final APIs purity is the first specification while yield is generally the priority for intermediates. Holodiag develops specific crystallization conditions aiming at yield or purity optimization.
Some molecules are sometimes only obtained as amorphous solid or even oily samples. High crystallinity materials generally yield improved properties (e.g. stability, flowability). Holodiag develops specific crystallization conditions aiming at higher cristallinity samples (e.g. slower cooling, salt cristallization).
Particle size and shape are parameters of great importance for processability and final product quality: filterability, residual solvent, powder compressibility, flowability and more. Holodiag develops specific crystallization conditions aiming at control of particle size and shape in order to meet specifications or improve processability (filtration, drying).
Control of solid state
Production of the selected crystal form is critical for API manufacturing. Based on existing knowledge (screening, literature), Holodiag develops robust and reproducible crystallization conditions for producing the target polymorphic form.
Access to pure isomer is a key step in API development while separation is often a challenging process. With in-depth expertise, Holodiag develops crystallization conditions for accessing pure isomers (e.g. cis/trans, Z/E, enantiomers). Enantiomer separation by crystallization can be developed from racemic or excess mixture, with or without resolving agent.
Filtration and drying
Filtration and drying of solids are often bottleneck steps for industrial production, mainly because of solid state and particles. Holodiag accurately depicts filtration and drying behavior, identifies root cause and adapts crystallization conditions to improve the total process.
Critical parameters and robustness
A process is fully completed with critical parameter identification and sufficient robustness for safe industrial production. With in-depth knowledge in crystallization phenomena, equilibria, thermodynamics and phase diagrams, Holodiag delevops processes with clear view on critical parameters and optimize robustness. Thus, development of crystallization process according to Quality by Design (QbD) strategy becomes a real option.