Extractive Crystallization of Cabotegravir in Droplet-based Microfluidic Devices

Abstract Monodisperse emulsions of solvent saturated with the active pharmaceutical ingredient (API) cabotegravir were generated by microfluidic devices. In contrast to model oil-water emulsions that provide idealized conditions for obtaining highly monodisperse emulsions, APIs impart strict limitations on solvent choice. To provide a suitable environment in which extractive crystallization could occur, and to enhance reproducibility, co-solvents were introduced. Subsequently, the effect of each solvent component on morphology and size was observed. Through the manipulation of solvent composition, particles of both plate-like and spherical multi-crystal agglomerates were obtained, providing the ability to tune the operating conditions to provide particles with desirable characteristics such as size, shape and flowability. Scale-up of the manufacturing process was addressed through the application of existing microfluidic parallelization techniques, resulting in a 100-fold increase in throughput over a single-channel device. Subsequently, the obtained pure, and excipient-bound, API spherical agglomerates, were subjected to batch isolation and washing.