Crystal Size Control in a Continuous Tubular Crystallizer

Abstract

This paper describes a simple model-free (i.e., empirical) control strategy for crystal size tuning in a continuously operated tubular crystallizer. The crystallizer is designed for a seeded cooling crystallization process and acetylsalicylic acid crystallization from an ethanol solution was used as model system. Using a crystal size distribution (CSD) analyzer and minor initial studies, we developed a feedback controller that accurately tuned the mean crystal size within the range of 90–140 μm. In addition, we created a cleaning concept for long-term runs based on a consistency study, which demonstrated that the CSD of the products remained robust when process settings were kept constant. Sufficiently small and uniform seed crystals were generated via ultrasound irradiation.

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

“…The particle size distribution (PSD) of the produced crystals affects downstream processes such as filtration, milling, and formulation [1,5]. Furthermore, the solubility, disintegration, and dissolution rate of medicines in the human body depend on this parameter [5,6].…”

“…The particle size distribution (PSD) of the produced crystals affects downstream processes such as filtration, milling, and formulation [1,5]. Furthermore, the solubility, disintegration, and dissolution rate of medicines in the human body depend on this parameter [5,6]. The batch processes, often used in industry, suffer from batch-to-batch variabilities in particle size distributions, growth rates, and crystal habits [1,2,7,8].…”

Continuous Suzuki—Miyaura reactions with novel Ce—Sn—Pd oxides and integrated crystallization as continuous downstream protocol

“…In particular, continuous Suzuki-Miyaura reactions were carried out in a packed-bed reactor and the product isolation was done by continuous antisolvent crystallization. Continuous crystallization is a common unit operation for the purification of organic compounds because of its high efficiency, and the low capital and operational costs [15]. In addition to large-scale batch and continuous crystallizers, numerous small-scale semibatch and continuous setups with high-intensity mixers and impeller jets have been reported in literature [16].…”

“…Furthermore, particle formation in flow-through devices with inner diameters of few centimeters has been reported. Our group published several studies focusing on the controlled growth of crystals by selecting precise cooling trajectories in continuous-flow crystallizers [15][16][17][18].…”

Crystal Population Growth in a Continuous Helically Coiled Flow Tube Crystallizer

“…Here, a HCT crystallizer was chosen as a novel device because of its compactness, flexible geometry, high heat exchange rates, and narrow residence time distribution (RTD). Coiled tubular crystallizers have been applied for crystal size control of active pharmaceutical ingredients by Khinast and co-workers [5][6][7][8]. The aim of this paper was to determine whether continuous shape-selective crystallization is possible in a HCT.…”