Process Development in Quality-by-Design Paradigm for Anti-Solvent Aided Crystallization: Impact of Crystallization Parameters on Particle Morphology and Dissolution Behaviour of Dexlansoprazole Active Pharmaceutical Ingredient

BACKGROUND: In this work, a process development study for the crystallization step of dexlansoprazole API has been demonstrated under the Quality-by-Design (QbD) paradigm. Dexlansoprazole (crystalline) samples prepared under different crystallization conditions of reactor temperature and addition time of anti-solvent were subjected to solid-state characterization with variety of analytical techniques, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapour sorption (DVS), scanning electron microscopy (SEM), particle size distribution (PSD) by laser diffraction and intrinsic dissolution rate (IDR). RESULTS: The crystalline samples were observed to have identical polymorphic phase integrity but differed in their physical characteristics. The particle size distribution and microscopy data collectively elucidated the particle growth kinetics and the extent of agglomeration could be correlated to crystallization conditions, namely reactor temperature and addition time of anti-solvent. The intrinsic dissolution rate of samples was in good agreement with the morphological properties. CONCLUSION: An empirical model has been proposed for intrinsic dissolution rate correlating with crystallization process parameters. In conclusion, it was possible to elucidate the impact of crystallization parameters on the solid-state behaviour of dexlansoprazole for development of appropriate pharmaceutical dosage forms. (c) 2024 Society of Chemical Industry (SCI).