UNDERSTANDING DYNAMICS IN THIN-FILM SPHERICAL CRYSTALLIZATION OF ACTIVE PHARMACEUTICAL INGREDIENTS FROM MICROFLUIDIC EMULSION

Abstract

In this thesis, detailed experimental studies of dynamics and morphological outcomes in thin-film spherical crystallization of glycine from microfluidic emulsions are presented, supported by a theoretical model developed based on concepts drawn from classical nucleation theory. Careful investigation of the entire spherical crystallization process is carried out, with the aim to strengthen our fundamental understanding of emulsion-based crystallization. Speci¿cally, process parameters like droplet size, shrinkage rate, and temperature are studied to understand and delineate their effects on spherical crystallization, thus identify crystallization conditions that yield compactly packed spherical crystal agglomerates. The gained understanding makes it possible to employ advantages of emulsion-based crystallization, such as precise control over crystal size, shape and polymorphic form (thereby eliminating the need for costly downstream dry milling and grinding), in industry settings. It paves a way for designing a novel continuous crystallization reactor for industrial scale manufacturing of APIs.