Abstract

Reaction and Particle Engineering in Flow: From Scalable, Intensified Chemistry to Designer Drug Products

Saif Khan, Associate Professor, Chemical and Biomolecular Engineering, National University of Singapore

Pharmaceutical manufacturing is conventionally divided into two parts - ‘primary manufacturing’, which involves making the drug substance (i.e. the Active Pharmaceutical Ingredient - API) via chemistry and ‘secondary manufacturing’, which involves formulating the drug substance for delivery to the patient. In this talk, I will provide an overview of our research on engineering micro- and milli-fluidic systems to develop advanced manufacturing processes that bridge both primary and secondary pharmaceutical manufacturing. First, I will discuss how such systems can enable both deeper kinetic understanding of multiphase chemistries as well as scalable, intensified reaction engineering. In particular, I will focus on the important case of metal-catalysed gas-liquid reactions, such as hydrogenations and oxidations, and discuss a novel class of triphasic segmented flow reactors that greatly intensify the chemistry while also enabling scalable manufacturing with complete catalyst recovery and recycle. Next, I will discuss how microfluidics-based processes are enabling new ways to envision the final drug product, by enabling precise control over the solid state of the drug substance. In particular, I will discuss a recently developed technique which allows for crystallization and formulation of drug substances to be carried out in a single processing step, leading to monodisperse spherical granules with unprecedented control over crystal attributes such as shape, size and polymorphism. This technique couples the usage of microfluidics for emulsion generation and thin film evaporative/cooling crystallization where, by tuning the various process parameters, we are able to crystallize and formulate a wide range of hydrophilic and hydrophobic model and commercial drugs into monodisperse spherical microparticles with tunable properties. These particles allow the realization of the idea of ‘drug product intermediates’ that bridge the traditional gap between primary and secondary manufacturing. In summary, I will discuss the challenges and opportunities in blurring the boundary between drug substance and drug product via microfluidics-based manufacturing processes.