Ultrasound Assisted Crystallization of Paracetamol: Crystal Size Distribution and Polymorph Control

Bhangu, Sukhvir Kaur; Ashokkumar, Muthupandian; Lee, Judy

doi:10.1021/acs.cgd.5b01470

Cited by 113 publications

(111 citation statements)

References 54 publications

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“…The PSDs measured in situ at the end of crystallisation and prior to isolation were found to be consistent with literature data for the case of ultrasound assisted crystallisation of paracetamol [81].…”

Section: Crystal Size Distributionsupporting

confidence: 87%

“…The PSD in this study was compared to previous studies on paracetamol by Bhangu S. K. et al [81] and with other organic materials which have been subject to ultrasonic irradiation (see Section S2 Supplementary data). The PSDs measured in situ at the end of crystallisation and prior to isolation were found to be consistent with literature data for the case of ultrasound assisted crystallisation of paracetamol [81].…”

Section: Crystal Size Distributionmentioning

confidence: 99%

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The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

et al. 2017

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Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol% solution of the selected impurity from 0.85 mol% to 0.35 mol% and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol% to 1.52 mol%.

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Section: Crystal Size Distributionsupporting

confidence: 87%

Section: Crystal Size Distributionmentioning

confidence: 99%

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

et al. 2017

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“…Form II shows better properties but is harder to obtain because under normal conditions only form I can be generated. Furthermore, form II transforms within 6 h at 0 °C to form I in solution [52]. The crystals produced here were grown for 2 h at 27 °C to 43 °C, which is considerable higher than the 0 °C mentioned by Bhangu et al Therefore, the transition of form II Furthermore, the XRD patterns of crystals produced at different supersaturations and power levels are given in Figure 8.…”

Section: Influence Of the Power Levelmentioning

confidence: 72%

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

et al. 2017

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Controlling particle size is essential for crystal quality in the chemical and pharmaceutical industry. Several articles illustrate the potential of ultrasound to tune this particle size during the crystallization process. This paper investigates how ultrasound can control the particle size distribution (PSD) of acetaminophen crystals by continuous seed generation in a tubular crystallizer followed by batch growth. It is demonstrated that the supersaturation ratio at which ultrasound starts seed generation has a substantial effect on the final PSD while the applied power is insignificant in the studied conditions. The higher the supersaturation ratio, the smaller the final crystals become up to a supersaturation ratio of 1.56. Furthermore, it was shown that ultrasound can also impact the final PSD when applied during the growth phase. Frequencies of 850 kHz or below reduce the final particle size; the lower the applied frequency, the smaller the crystals become. In conclusion, one could state that ultrasound is able to control the particle size during seed generation and subsequent growth until the final particle size.

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“…Kaur Bhangu et al studied the batch anti-solvent crystallization of paracetamol in ethanol-water [15]. Ultrasound significantly decreased the induction time, as well as the particle size, and even led to the formation of orthorhombic form II crystals in combination with the usually observed monoclinic form I.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism behind sonocrystallization remains unclear; however, most research suggests that the effects are most likely associated with acoustic cavitation. Acoustic cavitation can be divided into stable cavitation, which entails the formation, growth, and oscillation of microbubbles under the influence of ultrasound waves, and transient cavitation, in which these microbubbles also violently collapse [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process

et al. 2018

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Continuous crystallization in tubular crystallizers is of particular interest to the pharmaceutical industry to accurately control average particle size, particle size distribution, and (polymorphic) shape. However, these types of crystallizers require fast nucleation, and thus, short induction times at the beginning of the flow process, which is challenging for larger and complex organic molecules. High shear and/or the presence of bubbles were identified to influence the nucleation behavior. This work investigates the effects of both high-shear mixing and ultrasound on the anti-solvent crystallization of paracetamol in acetone-water. Both devices generate intense amounts of shear and gas bubbles. Generally, the results show that increasing input power decreases the induction time significantly for both the rotor-stator mixer and ultrasound probe. However, the induction time is almost independent of the supersaturation for the ultrasound probe, while the induction time significantly increases with decreasing supersaturation for the rotor-stator mixer. In contrast, the particle size distribution for the rotor-stator mixer is independent of the supersaturation, while increasing supersaturation decreases the particle size for the ultrasound probe.

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Ultrasound Assisted Crystallization of Paracetamol: Crystal Size Distribution and Polymorph Control

Cited by 113 publications

References 54 publications

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

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

Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process

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