Progress on drug nanoparticle manufacturing: exploring the adaptability of batch bottom-up approaches to continuous manufacturing

Abstract

Approximately 40 % of approved drugs and 90 % of small molecule drug candidates in development suffer from poor solubility, limiting their delivery and efficiency on site. Nanomanufacturing, particularly the production of drug nanoparticles and nanosuspensions, offers a solution by enhancing dissolution rates. However, traditional batch processes face challenges in particle size control, downstream processing, throughput, yield, and scalability. Continuous manufacturing (CM) presents a promising alternative, enabling the production of drug nanosystems in a streamlined, continuous scheme that reduces intermediate steps, footprint, and cost. CM also supports improved process control, real-time monitoring, and scalability through parallelization rather than traditional scale-up. This review examines recent advancements in adapting batch bottom-up technologies to continuous processes, focusing on the critical process parameters, critical material attributes and key quality attributes for nanoparticle production, integration of continuous methods, and the associated challenges of implementation in pharmaceutical manufacturing, including downstream processing, scale-up, and regulatory considerations.