A run-to-run control strategy for polymorphic transformation in pharmaceutical crystallization

Polymorphism is a phenomenon that a substance can have more than one crystal form, each with distinct characteristics. Consequently, controlling polymorphism in drug manufacturing industries are crucial in order to ensure consistent production of the desired polymorph. In this paper, a run-to-run concentration control (C-control) based on iterative learning control is developed. As a case study, a model of polymorphic transformation of L-Glutamic acid from metastable α-form to stable β-form, where the yield of β-form is to be maximized, is used to illustrate the proposed run-to-run C-control and its advantage over the conventional C-control.