Mechanistic Insights into Paracetamol Crystallization: Exploring Ultrasound and Hydrodynamic Cavitation with Quartz Crystal Microbalance Dissipation

IF 4.3 Q2 ENGINEERING, CHEMICAL
Madhumitha Dhanasekaran*, Varaha P. Sarvothaman*, Paolo Guida and William L. Roberts, 
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Abstract

Crystallization is a crucial process in the purification of active pharmaceutical ingredients (APIs). Achieving controlled and efficient crystal formation is vital in successful production for industrial applications. This study investigates the crystallization of paracetamol using a model system, focusing on two techniques: ultrasound cavitation (UC) and hydrodynamic cavitation (HC). The role of cavitation in enhancing crystallization is well-established by using ultrasound. However, the crystallization process utilizing HC, especially in the absence of an antisolvent, is not investigated. A detailed investigation is still necessary to understand the nucleation process at the molecular level. This work primarily focuses on forming paracetamol crystals in an aqueous medium without the need for an antisolvent in HC. To address the nucleation study at the molecular level, the quartz crystal microbalance with dissipation (QCM-D) technique was employed to explore the nucleation kinetics of paracetamol crystallization while the solution is cooling. QCM-D allowed for real-time monitoring of mass changes and viscoelastic properties on the sensor surface, providing valuable insights into the adsorption, growth, and dissolution kinetics of paracetamol crystals under the influence of both cavitation techniques. The study revealed distinct crystallization behaviors depending on the type and intensity of cavitation, shedding light on the underlying mechanisms and potential implications for pharmaceutical manufacturing and formulation. These findings indicate that high-quality crystals can be produced using HC without the need for an antisolvent. This work highlights the significant potential for improving the efficiency and control of paracetamol crystallization and plays an important role in scaling up the crystallization process using HC.

对乙酰氨基酚结晶的机理:用石英晶体微天平耗散探索超声和流体动力空化
结晶是活性药物成分纯化的关键过程。实现控制和有效的晶体形成对于工业应用的成功生产至关重要。本研究以超声空化(UC)和流体动力空化(HC)两种技术为研究对象,利用模型系统研究了扑热息痛的结晶过程。利用超声证实了空化作用对结晶的促进作用。然而,利用HC的结晶过程,特别是在没有抗溶剂的情况下,没有研究。要在分子水平上理解成核过程,还需要进行详细的研究。这项工作主要集中在不需要HC抗溶剂的情况下在水介质中形成扑热息痛晶体。为了在分子水平上进行成核研究,采用石英晶体耗散微天平(QCM-D)技术研究了溶液冷却时扑热息痛结晶的成核动力学。QCM-D可以实时监测传感器表面的质量变化和粘弹性,为两种空化技术影响下扑热息痛晶体的吸附、生长和溶解动力学提供有价值的见解。该研究揭示了不同的结晶行为取决于空化的类型和强度,揭示了潜在的机制和对药物制造和配方的潜在影响。这些发现表明,使用HC可以在不需要抗溶剂的情况下生产高质量的晶体。本研究在提高对乙酰氨基酚结晶效率和控制方面具有重要的潜力,对扩大HC结晶工艺具有重要作用。
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来源期刊
ACS Engineering Au
ACS Engineering Au 化学工程技术-
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期刊介绍: )ACS Engineering Au is an open access journal that reports significant advances in chemical engineering applied chemistry and energy covering fundamentals processes and products. The journal's broad scope includes experimental theoretical mathematical computational chemical and physical research from academic and industrial settings. Short letters comprehensive articles reviews and perspectives are welcome on topics that include:Fundamental research in such areas as thermodynamics transport phenomena (flow mixing mass & heat transfer) chemical reaction kinetics and engineering catalysis separations interfacial phenomena and materialsProcess design development and intensification (e.g. process technologies for chemicals and materials synthesis and design methods process intensification multiphase reactors scale-up systems analysis process control data correlation schemes modeling machine learning Artificial Intelligence)Product research and development involving chemical and engineering aspects (e.g. catalysts plastics elastomers fibers adhesives coatings paper membranes lubricants ceramics aerosols fluidic devices intensified process equipment)Energy and fuels (e.g. pre-treatment processing and utilization of renewable energy resources; processing and utilization of fuels; properties and structure or molecular composition of both raw fuels and refined products; fuel cells hydrogen batteries; photochemical fuel and energy production; decarbonization; electrification; microwave; cavitation)Measurement techniques computational models and data on thermo-physical thermodynamic and transport properties of materials and phase equilibrium behaviorNew methods models and tools (e.g. real-time data analytics multi-scale models physics informed machine learning models machine learning enhanced physics-based models soft sensors high-performance computing)
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