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The stirred-tank crystallizer (STC) is the widely used apparatus in industrial crystallization. However, it presents notable challenges, including a broad crystal size distribution (CSD) and fouling. Herein, the twisted hexagonal tube (THT) was employed for thiourea cooling crystallization. The THT exhibited superior heat transfer performance compared to the circular tube (CT) under identical conditions. Furthermore, the THT exhibited longer induction times and wider metastable zone width compared to STC and CT, indicating that the THT can effectively mitigate the nucleation rate. Crystals formed in the THT exhibited elliptical shapes, with a purity of 99.3 % and a target-product (425 μm) proportion of 78 wt%. Thiourea crystallized using the THT met the first-class in China standard HG/T 3454–2013, whereas those crystallized using STC and CT met the second-class standard. Consequently, the THT, as a novel tubular crystallizer, demonstrated considerable potential. [Display omitted] • Twisted hexagonal tube (THT) crystallizer was first time used for cooling crystallization. • THT has a higher heat-transfer efficiency in cooling crystallization compared with circular tube. • THT achieved highest target-product yield of 78 wt% with highest purity 99.3 %. [ABSTRACT FROM AUTHOR]

The control of size distribution is important as it determines the efficiency of downstream processes. The crystalline particles with a narrow size distribution can be produced by controlling the time for the formation of the first crystal. In this study, we investigated the effects of aeration on desupersaturaion to improve size distribution during cooling process. The results show that aeration was able to induce nucleation even in the temperature range where spontaneous nucleation does not occur under certain cooling rate conditions. Furthermore, fine crystals with a narrow size distribution were obtained using aeration. The enhancement effect of desupersaturation was dependent on the aeration start temperature. Therefore, to improve the size and size distribution of crystals, it is important to determine the suitable aeration start temperature. In summary, the characteristics of crystalline particles obtained when aeration is performed could be evaluated based on the changes in the supersaturation of the solution. [Display omitted] • Aeration was introduced into cooling crystallization to improve size distribution. • Aeration allowed the production of fine crystals with a narrow size distribution. • The enhancement effect of desupersaturation depends on the aeration temperature. • A suitable aeration temperature is important to improve the characteristics. [ABSTRACT FROM AUTHOR]

It was recently demonstrated that the technique of solid hollow fiber membrane-based cooling crystallization can be employed to achieve continuous polymer precipitation from a solution and subsequent polymer coating/encapsulation of sub-micrometer particles/drug crystals as well as nanoparticles in suspension. In this technique, there is no need for high pressure as in supercritical solvent-based anti-solvent crystallization; further, there is easy scale-up and production of free-flowing polymer-coated particles. There is a concern however, whether this crystallization method can be applied for an extended duration since the earlier studies were run for only about 10 min. In this work, the duration of the cooling crystallization-based coating process has been greatly extended from 10 min to 60 min and 120 min. Eudragit RL 100 was chosen as the coating polymer and Cosmo 55 (550 nm silica particles) was the host for the coating process in an acetone solution. Scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) were employed to characterize the coated samples. The results showed that the solid hollow fiber membrane-based cooling crystallization performed successfully as a continuous crystallizer during extended time running operation. Characterization of the products by SEM and TGA indicated a stable product consistent with a uniform spherical shape. The coating thickness of the samples tended to be essentially identical for the extended-duration coating process as long as solvent loss by volatilization and uneven distribution of host particles in the feed solution-suspension was kept to a minimum. Unlabelled Image • Continuous polymer coating of suspended submicron silica particles was demonstrated. • The technique uses solid hollow fiber membrane-based cooling crystallizer. • Coating thickness on silica particles was uniform over a 60 min-long operation. • 550 nm silica particles were coated with ~31.5 nm polymer coating of Eudragit RL100. • There was no evidence of fouling of hollow fiber lumen vis-à-vis coating process. [ABSTRACT FROM AUTHOR]

Spherical crystallization can be an important technological step in the production of a solid form active agent. By the production of spherical crystals, direct compression tablet making can be applied to the powder material. This method makes the tableting process quicker, shorter and more economical with reduced amounts of additives and a reduced number of technological steps. This way, the granulation method can be avoided, which is also advantageous for a moisture sensitive drug. In this paper, we presented Focused Beam Reflectance Measurement (FBRM) studies applied in the case of the non-typical spherical crystallization methods of the active pharmaceutical ingredient ambroxol hydrochloride. Spherical agglomeration and controlled cooling crystallization methods were carried out based on our previous studies regarding these methods and the crystal formation processes were investigated with FBRM probe. Critical agglomeration periods and other mechanisms, such as the breakage of the agglomerates and the precipitation of small particles, were investigated. Chord length values were observed continuously and samples were taken out in certain points of the crystallization. Particle size analysis was carried out in each case to obtain information on the particle size enlargement caused by the crystallization methods. With the application of light microscopic analysis, aspect ratio and roundness values were also determined to obtain pieces of information on the sphericity-changes of the particles throughout the crystallization and large improvements were presented either for these parameters (aspect ratio from ~ 1.7 to ~ 1.3; roundness from ~ 2.4 to ~ 1.5) and the mean particle size (from ~13 μm to 120–400 μm). Among others, it was revealed that after the spherical agglomeration method (SA), mostly crystal agglomerates were formed, while slow cooling crystallization with alternating temperature profile (ATP) yielded larger and probably harder individual crystals. [ABSTRACT FROM AUTHOR]

Combining cooling crystallization and antisolvent crystallization is advantageous as it not only enhances yield but also offers two manipulative variables to exercise greater control on the outcome of a crystallization process. This study investigates the combined cooling and antisolvent crystallization of l -asparagine monohydrate (LAM) from it's aqueous solution using isopropanol as antisolvent. Three well known cooling policies (cubic cooling, natural cooling, linear cooling) and three feeding policies that are inspired by these cooling policies are employed to investigate the effect of combined modes of operation on crystal yield and crystal size distribution (CSD). The resulting supersaturation profile for a combined mode is intuitive and can be construed by qualitative superposition of supersaturation profiles of individual modes. A significant enhancement in the yield has been observed in all combined modes compared to individual modes of crystallization. Similar to individual modes, the highest mean size was obtained by combining slow cooling and slow-antisolvent addition strategy. Further, a population balance model is developed for the combined cooling and antisolvent crystallization system and the model predicts the concentration and final CSD well for all the cases investigated. [ABSTRACT FROM AUTHOR]

Potassium chloride crystals are cubic, which often leads to caking and greatly limits their applications. This caking can be overcome by modifying the crystal shape toward sphericity. Spherical particles have a high anti-caking ability and flowability. In this work, spherical KCl particles were prepared using a simple cooling crystallization process designed to function without additives. Among the four main processes in the crystallization of spherical particles, i.e., nucleation, growth, agglomeration, and attrition, agglomeration is the greatest contributor to the formation of spherical KCl particles, which were prepared following the principle that the adhesion force must be larger than the dispersion force. The adhesion free energy between KCl particles and solvents (i.e., water, n -hexane, formamide, diazomethane, methanol, ethanol, ethyl acetate, ethylene glycol, and dimethyl sulfoxide) was calculated using the Lifshitz–van der Waals acid–base approach, and water was found to be the most appropriate solvent because of its attractive interaction with the crystals. According to the relationship between the adhesion force and dispersion forces, we found that the stirring rate should be lower than 1300 rpm. Additionally, the effects of stirring rate and cooling rate on the KCl products were investigated and optimized, and the optimal conditions were found to be 400–500 rpm and 10–15 min/ ° C, respectively. All of the spherical KCl products prepared under the optimal conditions show a better morphology, flowability, and anti-caking performance than the original crystals. [ABSTRACT FROM AUTHOR]

In this work, pyrolysis oil produced by the slow pyrolysis of pinewood was the feed solution for a freeze concentration study and cooling crystallization recovery of levoglucosan. Liquid-liquid extraction of water-soluble compounds was performed by adding water to the original pyrolysis oil with ratios of 1:1 and 1:5 water: pyrolysis oil (wt%), respectively. A two-step suspension freeze concentration was then performed with the 1:1 and 1:5 aqueous pyrolysis oils (AqPO) to concentrate the solutions. The efficiency of water removal from AqPO was assessed by measuring the ice yield and distribution coefficient of ice impurities. Levoglucosan recovery from a supersaturated 1:1 AqPO-water mixture was performed for 37.5 min and 60 min by cooling crystallization with an aging time of 60 min. The average recovery rate of levoglucosan was 24 wt% with mean levoglucosan crystal size of 831 μm. [Display omitted] • Pyrolysis oil obtained from the slow pyrolysis of pinewood. • Freeze concentration of 1:1 and 1:5 aqueous pyrolysis oil extract (AqPO). • Levoglucosan recovery by cooling crystallization from 1:1 AqPO. [ABSTRACT FROM AUTHOR]

Two-dimensional population balance model for continuous cooling crystallization of high aspect ratio crystals, including nucleation, size-dependent growth of the two characteristic crystal facets and binary breakage along the crystal length is developed and analysed. The population balance equation is solved numerically using the 2D quadrature method of moments. The behaviour of the crystallizer and the effects of kinetic and process parameters on the characteristics of the crystal size distribution are analysed by detailed numerical experimentation. The binary breakage is described by four breakage rate functions comparing their effects on the mean length and mean aspect ratio of crystals. The simulation results revealed several interesting phenomena caused by interactions of the nonlinear sub-processes playing a relevant role in formulation of high aspect ratio crystals. Interactions of nucleation and size-dependent breakage may induce decrease in production of crystals. Size-dependent crystal breakage, decreasing the mean length of crystals induces some increase in their mean width. [ABSTRACT FROM AUTHOR]