Modelling Solvent-Mediated Polymorphic Transitions during Cooling Solution Crystallization
| Authors: | Fevotte Gilles, Universite Lyon-1, France
Sheibat-Othman Nida, Universite Lyon-1, France |
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| Topic: | 8.4 Control of Biotechnological Processes |
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| Session: | From Drug Design to Production: Control Issues |
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| Keywords: | Partial differential equations, Dynamic modelling, Particulate processing, Product quality, Chemical industry, Crystallization, Polymorphism, Femlab |
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Abstract
Polymorphism is one of the most important issues raised by the industrial crystallization of Active Pharmaceutical Ingredients (API). The dynamic modelling of polymorphic transformations is developed using Femlab®, a multiphysics simulation software, which is applied to the resolution of the Populations Balance Equations (PBE) involved. The stable and metastable distinct populations of crystals are represented in a mono-dimensional framework (i.e. one particle size as internal variable.) The simulation reproduces experimental features associated with Ostwald’s Rule of Stages, it allows explaining and analysing the conditions of occurrence of both stable and metastable forms of the solid product.
