Particle Size Determination for Process Analysis

Abstract Particles and droplets are critical in the determination of product quality and process efficiency in the manufacture of a wide range of chemical, pharmaceutical, and biological products. Processes such as crystallization and precipitation, homogenization and emulsification, polymerization, and fermentation are based on the detailed understanding, optimization, and control of particles, droplets, and bubbles. This article distinguishes between in situ particle system characterization (PSC) and traditional off‐line particle size analysis (PSA), and explains how the broader view of PSC is better suited to optimization and control of complex multiphase processes. PSC goes beyond traditional off‐line PSA, to provide real‐time, in‐process measurements of the rate and degree of change in particles and particle structures as they exist in the actual process environment. In situ process analytical methods can also significantly reduce measurement errors associated with off‐line sampling and sample preparation. This facilitates improved process development through direct real‐time monitoring of the particles and droplets as they exist and change in process. Process‐analytical‐based understanding contributes to faster methods of optimization and results in more consistent scale‐up. Real‐time monitoring and control of the particle system in the manufacturing environment is also used as a tool to help assure product quality.