title: Multi-scale flowsheet simulation of an integrated continuous purification-downstream pharmaceutical manufacturing process.
abstract: Properties of active pharmaceutical ingredients influence the critical quality attributes (CQAs) of final solid dosage forms (e.g. tablets). In the last decade, continuous manufacturing has been shown to be a promising alternative to batch processing in the pharmaceutical industry. Therefore, a quantitative model-based analysis of the influence of upstream API properties on downstream processing quality metrics will lead to enhanced QbD in pharmaceutical drug product manufacturing (Benyahia et al., 2012). In this study, a dynamic flowsheet simulation of an integrated API purification step (crystallization), followed by filtration and drying, with a downstream process (powder mixing) is presented. Results show that the temperature profile of a cooling crystallization process influences the crystal size distribution which in turn impacts the RSD and API concentration of the powder mixing process, which in turn has a direct effect on tablet properties (Boukouvala et al., 2012). A hybrid PBM-DEM model is also presented to demonstrate the coupling of particle-scale information with process-scale information leading to enhanced elucidation of the dynamics of the overall flowsheet simulation.
authors: Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Maitraye
authors: M
authors: Sen
authors: Anwesha
authors: A
authors: Chaudhury
authors: Ravendra
authors: R
authors: Singh
authors: Joyce
authors: J
authors: John
authors: Rohit
authors: R
authors: Ramachandran
mesh_terms: D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003460:Crystallization; D004339:Drug Compounding; D005374:Filtration; D008962:Models, Theoretical