(224a) Recent Advances in Continuous Slug-Flow Crystallization

Continuous slug-flow crystallization is an approach for the manufacture of pharmaceutical crystals with improved control of product characteristics, simplified post-crystallization operations, higher production rate flexibility, and reduced capital costs and footprint. Explanations are provided for the reported order-of-magnitude reductions in secondary nucleation and production times compared to batch, semibatch, and mixed-suspension mixed-product-removal crystallizers. After reviewing the literature on slug/segmented-flow crystallization, recent advances are described in equipment design/configurations. Pros and cons of different process intensification strategies are discussed, such as (1) the spontaneous generation of hydrodynamically stable slug flow; (2) indirect vs. direct and spatially localized vs. spatially distributed ultrasonication, (3) dual-impinging jet, coaxial, and radial micromixers, and (4) operating micromixers under laminar vs. turbulent flow conditions. Guidance is provided for quickly assessing whether slug-flow crystallization is the appropriate technology for a particular solute-solvent(s) system and, if so, systematically select equipment configurations, design parameters, and control system designs.