Title : Strategy in crystallization process to ensure solid state stability of drug substance
Crystallization of pharmaceutical ingredients, primarily those that possess several polymorphic forms, particle size and morphology critical properties, are among the most serious and least understood manufacturing procedure. Many processes and product failures can be traced to a poor understanding or lack control of the crystallization procedures. Clearly the pharmaceutical industry requires to getting more competitive and robust process by the knowledge of molecular complexity and solid form challenges, due to the impact of material properties for production efficiency related to the solid implication on drug product formulation.The content of this presentation is focused on reporting real case examples from the lab and development scale to production, throughout in-process crystallization measurements and control by means also of PAT approaches. Process understanding using in-process techniques in development scale, such as automated batch reactor vessels equipped with Reaction Calorimetry, ATR/FT-IR Spectroscopy, Focus Beam Reflectance (FBRM) probes plus temperature and pH sensors, were suitable methods to reach the desired active ingredient requirements, and then define a suitable tool in control the Critical Quality Attributes with as well benefits in process cycle time reduction. A variety of in situ analytical methods applied, combined with chemometric tools for the analysis of multivariate process information, have provided a basis for future improvement in modelling, simulation and control of crystallization procedures. These on-line recorded data together with chemical properties parameters assessed by off-line controlling techniques, are the starting point for intended processes for high quality products.