Template-induced nucleation for controlling crystal polymorphism: from molecular mechanisms to applications in pharmaceutical processing

Abstract

Over the last two decades, the use of template surfaces to induce heterogeneous crystal nucleation has been explored primarily to address two different goals: first, as an alternative to the conventional seeding technique used for polymorph control and, second, as a technique to promote the nucleation rate in novel crystallisation processes and formulations. The former need conceivably arises due to the risk of crystallising a new polymorph despite pre-seeding the solution with the desired crystal form. In this context, we review ongoing efforts in the research area of template-induced crystallisation, covering both experimental and simulation studies directed towards deeper understanding of the underpinning mechanisms. In addition, we report on the use of template-induced crystal nucleation as a process intensification technology for formulating drug substances and as a technique for enabling nucleation and polymorphic control during continuous manufacturing of active pharmaceutical ingredients.