The use of ultrasound in the crystallization process of an active pharmaceutical ingredient

Belca, Lucija Majal; Ručigaj, Aleš; Teslić, Dušan; Krajnc, Matjaž

doi:10.1016/j.ultsonch.2019.104642

Cited by 24 publications

(24 citation statements)

References 28 publications

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“…Although significant progress has been made over the past two decades, there remain many problems regarding the design, optimization and control of seeding effects and processes, and a more accurate description needs to be studied and defined. Some issues that deserve attention are highlighted as follows: A seed is commonly simplified to one characteristic dimension with an overwhelming use of the mean seed size and CV during operation design and optimization, thus ignoring the growth characteristics of seed crystals (e.g., growth rate dispersion). ,, A seed is generally assumed to comprise an initial condition, and model-based optimization strategies often perform suboptimally because of the lack of accurate models and the uncontrollable operating disturbances caused by abrupt seed introduction. , The seeding technique still lacks a systemic optimization design and evaluation methodology, not only for seed preparation but also for the desired product CSD, , although some experiential and experimental methods have been presented. , Determining a method for developing seeding techniques that can satisfy or circumvent GMP requirements is a noticeable problem that is often ignored in the literature but is very important to enable industrialization. , …”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

“…Determining a method for developing seeding techniques that can satisfy or circumvent GMP requirements is a noticeable problem that is often ignored in the literature but is very important to enable industrialization. , …”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

“…For instance, there have been some strategies developed for solving the above problems in the past few decades. One method is to develop a specified production process that satisfies the GMP requirements and use this process to specifically produce the desired seed crystals. , Another solution is to develop new seeding strategies that can beneficially avoid or eliminate the need for GMP seed preparation. , With the improvement in product quality and regulatory requirements, it seems difficult to cope with the problems mentioned above using existing approaches. Without the sake of completeness, the following three topics can be used to categorize some progress that has been made in recent years and may be considered valuable directions toward improving existing seeding techniques or developing new technologies: The multiple-pass seeding technique is a potential alternative for improving the operating flexibility; this technique can be used to deploy seed recipes with different sizes and masses according to the optimized control strategies and then treats seeding as a processing variable with an adjustable degree of freedom (e.g., the dynamic seeding technique , ) for specified product-property control (e.g., CSD). New directions in the development of seeding strategies involve designing seed-loading modes, integrating external seeding techniques with auxiliary technologies (such as milling and gassing) and upstream or downstream operations, and mapping seed behavior by computational fluid dynamics (CFD) simulations to improve seeding effectiveness. New directions in the development of seeding-control approaches include the use of mechanistic, data-driven or hybrid modeling approaches, multiobjective optimization control techniques, and robust and intelligent control methodologies to improve the control level, robustness and intelligent management of the crystallization process. , …”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

“…13,107 • Determining a method for developing seeding techniques that can satisfy or circumvent GMP requirements is a noticeable problem that is often ignored in the literature but is very important to enable industrialization. 105,108 Considering the above problems, some potentially valuable topics for improving seeding techniques are summarized from the several following aspects.…”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

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Progress and Opportunities for Utilizing Seeding Techniques in Crystallization Processes

Zhang

Shan

Wang

et al. 2021

Org. Process Res. Dev.

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Seeding is a significant but challenging task for optimizing crystallization process operation, product quality, and process efficiency. With the development of modern crystallization technology, there have been considerable advancements in seeding techniques in recent years. This article elaborates on how seeds affect the crystallization process, clarifies the qualitative connection between seeding parameters, defines the variables and product quality attributes based on a variable-based causal graph, and analyzes various possible factors that result in seeding-technique failure based on an Ishikawa diagram. The development of seeding-technique studies and existing problems are then systematically reviewed and discussed based on the qualitative and quantitative characteristics of seeds and the factors that influence seeding efficiency. Based on extensive research accomplishments, the challenges and opportunities for utilizing seeding techniques are analyzed, and potentially valuable seeding-technique topics and directions for improving crystallization are presented. In addition, a framework to guide seed recipe design and optimization is defined by combining simulation and experimental verification.

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Section: Challenges and Opportunitiesmentioning

confidence: 99%

Section: Challenges and Opportunitiesmentioning

confidence: 99%

Section: Challenges and Opportunitiesmentioning

confidence: 99%

Section: Challenges and Opportunitiesmentioning

confidence: 99%

See 2 more Smart Citations

Progress and Opportunities for Utilizing Seeding Techniques in Crystallization Processes

Zhang

Shan

Wang

et al. 2021

Org. Process Res. Dev.

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“…used the power ultrasound in crystallization process to efficiently control the nucleation of an API, ticagrelor. [ 9 ]…”

Section: Introductionmentioning

confidence: 99%

Particle Size and Crystal Habit Modification of Active Pharmaceutical Ingredient Using Cooling Sonocrystallization: A Case Study of Probenecid

Chang

Hsieh

2021

Crystal Research and Technology

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This study uses a cooling sonocrystallization process to recrystallize an active pharmaceutical ingredient, probenecid, and to improve the crystal qualities such as crystal habit and particle size characteristics. To screen the appropriate solvent system, solubility data of probenecid in organic solvent are measured, reported, and correlated by van't Hoff equation. According to the measured solubilities and data acquired from literature, sonocrystallization experiments using solvents with acceptable theoretical recovery are performed. Owing to the satisfactory throughput, yield, and crystal qualities, ethanol is finally decided as the appropriate solvent system. The effect of operating parameters in sonocrystallization including the solution concentration, sonication intensity, sonication duration, and cooling rate using ethanol as the solvent is further studied. With applying power ultrasound, probenecid crystals with narrow size distribution, regular crystal habit, and mean size around 15 µm are successfully produced. Finally, crystal form and spectroscopic property of sonocrystallized sample and probenecid as received from the supplier are compared and confirmed consistent from the analytical results of powder X‐ray diffractometer and Fourier transform infrared spectroscopy.

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Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

Haghighizadeh,

Mahdavi,

Rajabi

2024

Chem Eng & Technol

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Continuous crystallization of pharmaceuticals has been in the center of attention during the past two decades, with a more focus on the large‐scale production of active pharmaceutical ingredients. The increasing demand for pharmaceuticals requires high‐throughput production of drug crystals with different solubilities, stabilities, shapes, habits, polymorphs, and size distributions. With numerous advantages including low cost, ease of scale‐up, and superior control over polymorph and size distribution of drug crystals, antisolvent crystallization is one of the most promising crystallization methods recently attempted. However, it fails to deliver the required characteristic where the crystal systems tend to grow and for the preparation of metastable polymorphs. This review focuses on the most recent efforts to tackle these drawbacks by coupling antisolvent crystallization with cooling, supercritical‐assisted, microfluidics‐assisted, and membrane‐assisted crystallization. This systematic review aims to provide a concise summary of each coupled antisolvent technique and their positive and negative aspects. This review can be used as a guideline for pharmacist, biologists, and chemists, who are interested in the crystal engineering of pharmaceuticals to pave the way for further developments in this field.

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The use of ultrasound in the crystallization process of an active pharmaceutical ingredient

Cited by 24 publications

References 28 publications

Progress and Opportunities for Utilizing Seeding Techniques in Crystallization Processes

Progress and Opportunities for Utilizing Seeding Techniques in Crystallization Processes

Particle Size and Crystal Habit Modification of Active Pharmaceutical Ingredient Using Cooling Sonocrystallization: A Case Study of Probenecid

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

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