Rapid sonocrystallization in the salting-out process

Li, Hong; Wang, Jingkang; Bao, Ying; Guo, Zhihua; Zhang, Muyan

doi:10.1016/s0022-0248(02)01941-3

Cited by 150 publications

(127 citation statements)

References 5 publications

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“…This corresponds to a crystallization process with a very high collision frequency in which aggregation is effectively reverted before agglomeration can occur. An alternative approach to increase the number of collisions without addition of high seed loads is prompt generation of crystals [17,43,44]. Hence, quasi-instantaneous generation of a large number of crystals will increase the collision frequency, rapidly deplete the supersaturation and therefore reduce agglomeration.…”

Section: Prompt Generation Of Nucleimentioning

confidence: 99%

“…In addition, the massive increase in surface area will deplete the supersaturation within a shorter time frame, similar as the effect of micromixing. This inhibits the cementation of these aggregates and moves the process quickly into a growth-dominated regime [17,43,44]. In this stage, new crystalline material will be deposited on the surfaces of the priory formed crystals.…”

Section: Targeted Ultrasonic Treatment At Seeding Temperaturementioning

confidence: 99%

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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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Section: Prompt Generation Of Nucleimentioning

confidence: 99%

Section: Targeted Ultrasonic Treatment At Seeding Temperaturementioning

confidence: 99%

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

et al. 2017

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“…Particles collide with each other with such great force, which is responsible for breaking of particles. The magnitude of energy and time of exposure play the major role in the breakdown of particles and in obtaining particles of desired micromeritics (13). However, melting and rapid cooling offers the opportunity for the formation of irregular agglomerates of PRG during melting and MSC technique.…”

Section: Particle Size Analysismentioning

confidence: 99%

“…Application of ultrasound during crystallization leads into uniform mixing, which results in homogenous growth of crystals with low variation in particle size and morphological characteristics. Due to its effect on initial nucleation process, it reduces the width of metastable zone and initiates the process of nucleation at lower level of supersaturation (11)(12)(13). In our previous study, we obtained porous ibuprofen and celecoxib particles by use of melt sonocrystallization (MSC) technique (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Study of Polymorphs of Progesterone by Novel Melt Sonocrystallization Technique: A Technical Note

et al. 2010

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Abstract. A large number of pharmaceuticals exhibit polymorphism; 23% steroids, 60% sulfonamides, and 70% of barbiturates have shown this property. In this study, we have investigated and compared a new technique termed as melt sonocrystallization (MSC) with melt and sonocrystallization (SC) for induction of polymorphism in progesterone (PRG). Polymorphs were characterized by DSC, XRD, FT-IR, and FT Raman spectroscopy. Melt sonocrystallized progesterone (MSC-PRG) contained both the polymorphs, more soluble form II along with less soluble form I, whereas melt progesterone (M-PRG) and sonocrystallized progesterone (SC-PRG) contained only form I. Improvement in dissolution characteristics of both the polymorphs were compared and form II was found to be more readily soluble than form I in deionized water. Reduction in mean particle size of PRG during SC was also determined using laser diffractometer. During stability testing (40°C/75% RH) for 1 month, metastable form II of MSC-PRG was found to be transformed into its more stable state. MSC technique was thus found as a useful tool for induction of polymorphism.

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“…These methodologies avoid separate process steps such as dry milling, and they are considered attractive in drug development. Ultrasound has been shown to increase the nucleation rate of organic molecules (13)(14)(15)(16)(17) when compared to experimentation carried out without ultrasound (control) and, therefore, produces smaller particle sizes with narrower size distributions.…”

Section: Introductionmentioning

confidence: 99%

Towards Integrated Drug Substance and Drug Product Design for an Active Pharmaceutical Ingredient Using Particle Engineering

2011

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Abstract. A novel experimental approach describing the integration of drug substance and drug production design using particle engineering techniques such as sonocrystallization, high shear wet milling (HSWM) and dry impact (hammer) milling were used to manufacture samples of an active pharmaceutical ingredient (API) with diverse particle size and size distributions. The API instability was addressed using particle engineering and through judicious selection of excipients to reduce degradation reactions. API produced using a conventional batch cooling crystallization process resulted in content uniformity issues. Hammer milling increased fine particle formation resulting in reduced content uniformity and increased degradation compared to sonocrystallized and HSWM API in the formulation. To ensure at least a 2-year shelf life based on predictions using an Accelerated Stability Assessment Program, this API should have a D [v, 0.1] of 55 μm and a D [v, 0.5] of 140 μm. The particle size of the chief excipient in the drug product formulation needed to be close to that of the API to avoid content uniformity and stability issues but large enough to reduce lactam formation. The novel methodology described here has potential for application to other APIs.

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Rapid sonocrystallization in the salting-out process

Cited by 150 publications

References 5 publications

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

Study of Polymorphs of Progesterone by Novel Melt Sonocrystallization Technique: A Technical Note

Towards Integrated Drug Substance and Drug Product Design for an Active Pharmaceutical Ingredient Using Particle Engineering

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