Particle formation: Promise and challenges

Abstract

Particle formation establishes fundamental particle attributes at the initiation of an overall particle production process. These attributes include particle size distribution, particle morphology, crystal form, and defect level. These fundamental properties, in turn, affect downstream particle processing and product performance properties, including rate of drying, filterability, flowability, caking tendency, rate of dissolution, and for biologically active products bioavailability. Almost always, the goal is that the properties established at formation will provide excellent performance all the way through downstream processing, product formulation, and ultimate use of the product. However, meeting this goal is often not possible for a variety of reasons. First, it may be difficult, prohibitively expensive, or even impossible to achieve the desired properties during formation. Second, there are often conflicting requirements at different stages of production and use. For example, large equant particles may be desired for good filterability and flowability through downstream process steps, but very small particles may be required in the ultimate product application. Examples from the chemical and pharmaceutical industries are presented: both cases successfully producing particles with properties meeting the needs throughout the chain of downstream processing and final application, as well as cases where it was impossible to meet those requirements. For the latter, the additional processing or adaptations required for the product to succeed are outlined. The focus here is on additive particle formation, e.g. crystallization and precipitation from solution, and not subtractive particle formation, e.g. milling. Legacy of Reg DaviesI was fortunate enough, as a budding industrial crystallization engineer, to be invited by Reg to join the newly formed PARticle Science And Technology PARSAT group at DuPont. Reg recognized and documented the importance of particle technology to a large, diverse chemical and materials company like DuPont and PARSAT was to become a leading industrial particle technology group. Reg's vision was to combine the fundamental particle unit operations into a unified, comprehensive technology organization that would address the formation and processing of particles from process concept through end use.This paper describes the first step in many particle processes: particle formation. Reg's legacy vis a vis particle formation is the recognition that particle formation is a critical, foundational process in an overall process train that ultimately produces useful particulate products and intermediates, but that particle formation is nonetheless but one part of the overall process. It may be able to produce particles exactly as needed for end use performance, or additional processes may be needed to tailor particles for their ultimate use. In addition, intermediate processes may be required to preserve useful properties developed during formation but subject to degradation in subsequent operations.Finally, Reg served as inspiration and mentor for everyone in his orbit, and we are far better scientists and engineers for it.