Effects of operating conditions on agglomeration and habit of paracetamol crystals in anti-solvent crystallization

Yu, Zai Qun; Tan, Reginald B. H.; Chow, Pui Shan

doi:10.1016/j.jcrysgro.2005.02.050

Cited by 92 publications

(75 citation statements)

References 33 publications

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“…Elaborate procedures for controlling the rate of cooling or solvent evaporation during seeding have been recommended to manage polymorph production. Recent work by Yu (2003) indicates that classical concepts of crystallization are insufficient to describe polymorph nucleation phenomena. Cooling a crystal melt can nucleate a less stable polymorph on which a more stable polymorph can grow, and seeding with a particular polymorph can promote growth of another polymorph.…”

Section: Polymorphic Crystallizationmentioning

confidence: 99%

“…Anti-solvent crystallization has also been used to control particle size distribution during the crystallization of sodium chloride (Doki et al, 2002) and for the crystallization of paracetamol (Granberg et al, 1999;Fujiwara et al, 2002). The effect of agitation, feeding rate, and the evolution of the particle mean size has been reported for the anti-solvent crystallization of paracetamol with a water-acetone mixture (Yu et al, 2005). The continuous distribution model can be applied to anti-solvent crystallization by including in Equations (3c) and (4b) the rate of anti-solvent addition in V(t).…”

Section: Future Applicationsmentioning

confidence: 99%

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Cluster Kinetics of Phase Transitions: Applications to Innovative Technologies

McCoy

Madras

2008

Chemical Engineering Communications

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Phase transitions are critical in many of the new technologies of interest to chemical engineers. Applications to materials processing and pharmaceuticals manufacture are among the uses for phase transition dynamics investigated with the methods of population balance modeling for clustering processes. The underlying phenomenon of clustering occurs during condensation processes such as crystallization from solution. Self-assembly of molecules or supramolecules is likewise spontaneous clustering, often through non-covalent interactions. Vapor-liquid and solid-liquid condensations usually involve nucleation from a metastable state, accompanied by particulate growth and Ostwald ripening (with denucleation). The nucleation process is bypassed under certain conditions, such as in spinodal decomposition, glass transition, and gelation. It is proposed that the unifying concept for all these transformations is cluster kinetics and dynamics. Using population balance modeling, we outline how phase transition processes can be quantitatively modeled by cluster size distributions evolving in time. We also discuss how generic cluster processes apply to granular systems, synchronizing oscillators, and polymorphic transformations.

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Section: Polymorphic Crystallizationmentioning

confidence: 99%

Section: Future Applicationsmentioning

confidence: 99%

Cluster Kinetics of Phase Transitions: Applications to Innovative Technologies

McCoy

Madras

2008

Chemical Engineering Communications

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“…In terms of flowability, filterability and compaction properties, agglomerated particles can exhibit a clear benefit over single crystals, depending on the final morphology. In contrast, significant disadvantages such as reduced purity due to entrapment of mother liquor or other impurities, elevated generation of fines during transport and lower dissolution rate have been reported [11].…”

Section: Introductionmentioning

confidence: 99%

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

et al. 2017

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Application of ultrasound during crystallization can efficiently inhibit agglomeration. However, the mechanism is unclear and sonication is usually enabled throughout the entire process, which increases the energy demand. Additionally, improper operation results in significant crystal damage. Therefore, the present work addresses these issues by identifying the stage in which sonication impacts agglomeration without eroding the crystals. This study was performed using a commercially available API that showed a high tendency to agglomerate during seeded crystallization. The crystallization progress was monitored using process analytical tools (PAT), including focus beam reflectance measurements (FBRM) to track to crystal size and number and Fourier transform infrared spectroscopy (FTIR) to quantify the supersaturation level. These tools provided insight in the mechanism by which ultrasound inhibits agglomeration. A combination of improved micromixing, fast crystal formation which accelerates depletion of the supersaturation and a higher collision frequency prevent crystal cementation to occur. The use of ultrasound as a post-treatment can break some of the agglomerates, but resulted in fractured crystals. Alternatively, sonication during the initial seeding stage could assist in generating nuclei and prevent agglomeration, provided that ultrasound was enabled until complete desupersaturation at the seeding temperature. FTIR and FBRM can be used to determine this end point.

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“…The challenges involved in controlling crystallization are significant, since the kinetic parameters of the process are strongly affected by several factors such as the presence of impurities (Gunawan et al, 2002;Ma et al, 1999;Rauls et al, 2000;Poddar, 2002), breaking of crystals (Kougoulos et al, 2005;Gahn & Mersmann, 1995) and clustering (Yu et al, 2005;Paulaime et al, 2003) among other effects that are difficult to characterize.…”

Section: Introductionmentioning

confidence: 99%