Composite Preparation via Nanoparticle Assembly during Simultaneous Crystallization of Two Drugs

Developing effective combination drug therapies with enhanced control over drug properties is critical for improving patient outcomes. This study explores a novel approach to producing composite crystals of valsartan and amlodipine besylate via nanoparticle assembly through reverse antisolvent crystallization. The method involves controlled injection of drug solutions into an antisolvent, manipulating parameters like injection sequence and timing to influence the resulting crystal properties. Results demonstrate that the injection order significantly impacts the crystal structure and drug release kinetics of the composite particles. Specifically, amlodipine injection timing plays a crucial role in crystal growth and interaction with valsartan. Furthermore, postcrystallization after injection promotes the formation of stable amlodipine monohydrate crystals within the composite particles. Observed differences in release behavior suggest that drug phases locate in different regions within the composite particles, depending on the injection order. This work provides insights into engineering composite drug particles with tailored properties, offering a promising new route for developing more effective pharmaceutical formulations.