Industrial Perspectives of Pharmaceutical Crystallization

Industrial practice of pharmaceutical crystallization is reviewed in this manuscript through three levels of perspectives. The first level addresses the thermodynamic properties, which include basic properties such as solubility, crystal form, and morphology. The second level addresses the transport properties and rate behavior of crystallization, specifically kinetics of crystallization and mixing within a uniform suspension environment. Factors such as seeding, control of supersaturation, mixing time, and mixing intensity are discussed at this level. The third level addresses the overall process dynamics and scale-up issues. The main focus is on the rate and transport phenomena in a nonuniform suspension environment. Topics of mixing distribution and crystallizer design are addressed here. Specific examples are cited to demonstrate the impact of these factors on the design and performance of crystallization process.