Purnima N Manghnani, Ariel Yi Hui Chua, Serene Ming En Chong, Arif Z Nelson, Saif A Khan, Patrick S Doyle
Long-acting drug delivery systems depend on crystalline suspensions with tightly controlled particle size to ensure reliable delivery and long-term stability, yet producing sub-10μm crystals with narrow and persistent size distributions remains challenging. Here we introduce a bottom-up crystallization strategy in which monodisperse, pH-switchable structured emulsions act as transient microreactors that template active pharmaceutical ingredient microcrystals during anti-solvent crystallization. Confinement of droplets within a yield-stress soft-matter matrix enables the formation of highly uniform naproxen microcrystals (∼7μm). In contrast to conventional wet-bead milling, the resulting suspensions exhibit substantially reduced Ostwald ripening under accelerated stability conditions while preserving crystal form and injectability-relevant size. The method is readily scalable via membrane emulsification and supports downstream solid dosage formats, demonstrated by redispersible thin films. Together, this work establishes structured emulsions as a generalizable platform for engineering stable, monodisperse crystalline suspensions for long-acting drug delivery.