Partial Seeding Policy for Controlling the Crystal Quality in Batch Cooling Crystallization

Unno, Joi; Hirasawa, Izumi

doi:10.1002/ceat.201900618

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…In industrial crystallization, seeding is used for inducing and controlling secondary nucleation and crystal growth. A small quantity of seed crystals is added to induce secondary nucleation, while the seed crystals abundantly added could inhibit secondary nucleation and serve as the substrates for the growth of new branching because of a more favorable nucleation mechanism on the crystal growth interface. , It has been reported that secondary nucleation of ZnO branches occurred on the ZnO seeds with a high density of line defects that served as pinpoints for the secondary nucleation to occur. , Then, we tried introducing a sufficient quantity of crystal seeds with irregular morphology and rough surfaces (1 g, 10 wt %, Figures a and S8) to the solution system as the substrates of noncrystallographic branching and spherulites. As shown in Figure b,c, new branching nucleated directly on the surfaces of crystal seeds under agitation (150 rpm) during the aging period.…”

Section: Resultsmentioning

confidence: 99%

Spherulitic Growth Strategy for Agitation-Induced Formation of Spherical Amoxicillin Sodium Products

Cui

Yang

Yin

et al. 2022

Ind. Eng. Chem. Res.

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In industrial crystallization, spherical crystals have gained increasing interest due to their excellent physicochemical properties, such as high bulk density, flowability, stability, etc. However, their formation mechanism is still not well understood and is often oversimplified. In this work, spherical amoxicillin sodium crystals were obtained via a spherulitic growth strategy. It was found that agitation immediately after the addition of crystal seeds was critical for inducing radial noncrystallographic branching and spherulite formation of amoxicillin sodium. Without agitation during the aging period after seed addition, only discrete rodshaped crystals were obtained. The formation mechanism of amoxicillin sodium spherulites was studied using process analytical technology (PAT) tools, including focused beam reflectance measurement (FBRM) and particle video microscope (PVM). The result was indicative of a three-step morphological evolution process: formation of polycrystalline agglomerates, noncrystallographic branching, and spherulite growth. During this process, agitation immediately after seed addition could help to solute diffusion and induce the agglomeration of small crystals that result from secondary nucleation. The polycrystalline agglomerates serve as the cores for further noncrystallographic branching and growth. On this basis, a new spherulitic growth strategy was proposed by the large addition of crystal seeds as the growth substrates of new branching and spherulite growth. High agitation rates during the aging period can increase the mass ratio of spherulites, and high initial supersaturation can promote branching. Compared with the discrete rod-shaped crystals, spherulites self-regulate the final size greatly up to three times and have a higher bulk density as well as much lower hygroscopicity.

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Section: Resultsmentioning

confidence: 99%

Spherulitic Growth Strategy for Agitation-Induced Formation of Spherical Amoxicillin Sodium Products

Cui

Yang

Yin

et al. 2022

Ind. Eng. Chem. Res.

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“…In achieving the desired target, such as uniform CSD, seeding crystallization may offer a better option (Unno and Hirasawa, 2020), particularly for obtaining the large size of crystals (Lee et al, 2019), lessening supersaturation level and suppressing secondary nucleation leading to narrow CSD and high purity of crystals (Penha et al, 2019).…”

Section: Considerablementioning

confidence: 99%

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

Adnan

Samad

2022

ASEAN J. Chem. Eng.

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The driving force of the cooling crystallization process is supersaturation, where the supersaturation level during the crystallization process is crucial to grow the crystal sufficiently. Nucleation and crystal growth rates are two concurrent phenomena occurring during crystallization. Both are supersaturation functions that determine the growth of seed crystals and the formation of fine crystals. Trade-offs between nucleation and crystal growth are essential for achieving the large size of seed crystals with the minimum number of fine crystals. Thus, the objective of this study is to analyze the effects of nucleation and crystal growth rates on final product quality, which is crystal size distribution (CSD). Modeling of the crystallization process using a potash alum case study is highlighted and simulated using Matlab software. Then, the effects of nucleation rate, crystal growth rate, and both nucleation and crystal growth rates on CSD are evaluated using local sensitivity analysis based on the one-factor-at-a-time (OFAT) method. Based on simulation results for all strategies, a low combined rate delivers the best performance of the final CSD compared to others. Its primary peak has a mean crystal size of 455 µm with 0.0078 m3/m volume distribution. This means that the grown seed crystals are large with high volume distribution compared to the nominal strategy, which is at the mean crystal size of 415 µm and 0.00434 m3/m. Meanwhile, the secondary peak has the mean crystal size of 65 µm, 0.00028 m3/m in volume distribution. This corroborates the least number of fine crystals at the considerably small size compared to nominal’s (0.00151 m3/m, 35 µm). Overall, the low nucleation and crystal growth rates strategy provides useful insights into designing temperature profiles during the linear cooling crystallization process, whereby achievable supersaturation levels in obtaining large crystals with fewer crystal fines are provided via simulation.

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Linearized Parameter Estimation Methods for Modeled Crystallization Phenomena Using In-Line Measurements and Their Application to Optimization of Partially Seeded Crystallization in Pharmaceutical Processes

Hirasawa

Unno

Masaki

2022

Optimization of Pharmaceutical Processes

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Partial Seeding Policy for Controlling the Crystal Quality in Batch Cooling Crystallization

Cited by 6 publications

References 30 publications

Spherulitic Growth Strategy for Agitation-Induced Formation of Spherical Amoxicillin Sodium Products

Spherulitic Growth Strategy for Agitation-Induced Formation of Spherical Amoxicillin Sodium Products

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

Linearized Parameter Estimation Methods for Modeled Crystallization Phenomena Using In-Line Measurements and Their Application to Optimization of Partially Seeded Crystallization in Pharmaceutical Processes

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