Controlled nucleation of crystallization process as an efficient tool to tune the properties of corticosteroid API

Abstract

Crystallization as one of the final steps in the industrial production of active pharmaceutical ingredients (APIs) significantly influences their physicochemical and rheological properties. Different crystallization procedures including antisolvent crystallization, seeding crystallization, crystallization with templates and sonocrystallization were utilized for the production of corticosteroid APIs—fluticasone propionate. The final crystalline APIs obtained by individual crystallization procedures were characterized by a wide range of characterization techniques. We show that nucleation is a critical step that significantly affects APIs' properties. Controlled nucleation thus represents an easy method for managing these properties. Well-designed nucleation yields to crystalline products, which does not necessitate any post-processing including, e.g., micronization. These findings can be widely applied to the production of API with targeted properties.