Search

The solution-mediated polymorphic transformation (SMPT)of l-glutamic acid is modeled using the method of moments(MoM) with the addition of a dissolution term to account for the transformationof the metastable to the stable polymorph. The numerical solutionmethodology involves the kinetics of nucleation, growth, and dissolutionfor the polymorphic system. The effects of the cooling profile, initialsolute concentration, and seeding conditions on the product qualitywere investigated. In supersaturated solutions with respect to bothpolymorphs, the natural cooling yielded the highest mass of the metastableform, while the nonlinear cooling resulted in the highest mass ofthe stable form (13.41 g/kg of solvent). The ratio of the stable tometastable form masses was higher with the higher cooling rate parameters.In solutions supersaturated with respect to the stable form and undersaturatedrelative to the metastable form, the dissolution of the metastableform favored the production of the stable form. The number-weightaverage size of the stable particles was 148.5 μm with the nonlinearcooling policy which was 51% and 134% more than those correspondingto the linear and natural cooling policies. Finally, nonlinear programming(NLP) was used in a dynamic mode to investigate the optimal controlof the process with different objective functions. It was shown thatthe optimal control policy had a favorable effect on the yield ofthe stable or metastable form as well as the particle sizes at theend of the batch. The optimal control using an objective functionto maximize the mass of the metastable form at the end of the batchresulted in 7.8 g of crystals/kg of solvent for metastable form whichwas 33% and 381% higher than the natural and linear cooling policies.For an objective function to maximize the mass of the stable form,the optimal cooling policy increased the mass of the stable form by3.2% compared to the nonlinear cooling policy. [ABSTRACT FROM AUTHOR]