Towards achieving a flattop crystal size distribution by continuous seeding and controlled growth

Jiang, Mo; Wong, Min Hao; Zhu, Zhilong; Zhang, Jieqian; Zhou, Lifang; Wang, Ke; Versypt, Ashlee N. Ford; Si, Tong; Hasenberg, Lisa M.; Li, Yao En; Braatz, Richard D.

doi:10.1016/j.ces.2011.12.033

Cited by 47 publications

(48 citation statements)

References 31 publications

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“…In the experimental study that demonstrated the nucleation of crystals by mixing hot and cold saturated solutions [6], the Reynolds number indicates that the flow was in a laminar regime, which is the regime of interest in this article. As an example, the Reynolds number at the exit, Re = rUL/m, is on the order of 600 (using jet velocity v z and inner diameter 2r 0 , with density and dynamic viscosity values in Table 2) or smaller [17].…”

Section: Assumptions With Justifications For Deriving An Analytical Smentioning

confidence: 98%

“…The corresponding boundary conditions for concentration c(r, z) are @c @r ð0; zÞ ¼ 0; cðr; 1Þ ¼ c hot ¼ 0:20 g LAM=g water; cðr; À1Þ ¼ c cold ¼ 0:03 g LAM=g water; (6) where some example concentration values are given. For both the heat and mass transfer Eqs.…”

Section: Assumptions For Calculation Of Temperature and Concentrationmentioning

confidence: 99%

“…The relation between the solubility of LAM in deionized (DI) water (c sat , in g LAM/g water) and temperature (T, in C) is c sat = 3.084 Â 10 À2 T À 1.373 Â 10 À3 T + 5.214 Â 10 À5 T 2 [6]. Thus the solubility of LAM at the average mixing temperature (approximately 47.5 C, the average of the temperatures of two streams) is about 0.08 g LAM/g water.…”

Section: Physical Properties Valuesmentioning

confidence: 99%

“…Rather than anti-solvent crystallization as commonly used, a cooling DIJ mixer was recently demonstrated that combined hot and cold saturated solutions under laminar flow conditions to generate small uniform seed crystals of an organic compound [6]. All of the crystals from the cooling DIJ mixer were about 10 mm in length, placing them in the approximate size range for direct application in inhalers [7].…”

Section: Introductionmentioning

confidence: 99%

“…Theoretically, if the mixing was perfect (that is, solution concentrations and temperature were completely mixed at the molecular scale in the mixer), the average supersaturation level in Ref. [6] was too low to nucleate the crystals in a cooling DIJ mixer. The surprising result of nucleating crystals by combining hot and cold saturated solutions in a DIJ mixer motivates the theoretical analysis of the system in this article.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Understanding temperature-induced primary nucleation in dual impinging jet mixers

Jiang

Braatz

2015

Chemical Engineering and Processing: Process Intensification

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Section: Assumptions With Justifications For Deriving An Analytical Smentioning

confidence: 98%

Section: Assumptions For Calculation Of Temperature and Concentrationmentioning

confidence: 99%

Section: Physical Properties Valuesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Understanding temperature-induced primary nucleation in dual impinging jet mixers

Jiang

Braatz

2015

Chemical Engineering and Processing: Process Intensification

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Continuous Crystallisation

Brown

McGlone

Florence

2017

Continuous Manufacturing of Pharmaceuticals

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Mixing 2) Nucleation 3) Growth 4) Filter/wash/dry Required to:  Produce consistent composition  Control crystallisation driving force  Influence flow rate, shear-kinetic effects  Consistent suspension of seed and product Controlled via:  Supersaturation  High shear  External fields, e.g. ultrasound, nonphotochemical laser induced nucleation  Seed. Seeds produced via dry milling, wet media milling, precipitation, recycle, dissolution, spray drying or secondary nucleation Controlled to avoid:  Fouling  Agglomeration  Dissolution  Crystalline form transformation(s) Controlled via:  Supersaturation (typically low) via cooling, anti-solvent, evaporation  Effective heat/mass transfer Ensures:  Efficient desupersaturation Controlled to avoid:  Fouling  Agglomeration  Attrition (particle breakage)  Dissolution  Crystalline form transformation(s) Required to:  Create filter cake  Remove mother liquor and impurities  Maintain particle attributes Controlled to avoid:  Agglomeration  Attrition (particle breakage)Continuous crystallisation has been implemented for many decades in other manufacturing sectors, typically for large volume commodity chemicals, and offers a range of potential advantages [16,17] including lower operating and capital costs, reduced down time and more efficient use of energy and materials. Cooling and anti-solvent crystallisation are commonly used in industrial applications and can be readily implemented in continuous. The aim is to follow a controlled trajectory through the solubility phase diagram (section 1.2).

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