Design of the spherical agglomerate size in crystallization by developing a two‐step bridging mechanism and the model

Abstract

Spherical agglomeration technology can produce high‐performance spherical particles in a single crystallization unit, although it is still challenging to control the particle size and shape. To solve this issue, a two‐step bridging (TSB) mechanism containing a preconditioning period, size period, and shape period is proposed. The dynamic balance among the forces of adhesion, dispersion, and capillary action in the multi‐liquid phases plays a key role. This is fully considered to establish the TSB‐based thermodynamic size model and particle design framework by weighting the force action regions in multi‐liquid phases with dynamic composition. The spherical agglomerates of benzoic acid, celecoxib, and salicylic acid with narrow particle size distributions and tunable particle size ranges of 2000–5000, 800–3500, and 1500–4500 μm, respectively, were designed and prepared successfully, showing good correlation with the calculation, which is superior to the reported methods and indicates that the mechanism has certain universality and guiding significance.

Spherical agglomeration of high melting point drugs in water at low temperature by developing a two-step oiling-out mechanism and the design strategy

“…In the case of celecoxib, traditional granulation and spherical agglomeration technologies are now commonly used by researchers to prepare celecoxib spherical particles. 22,65 However, in the traditional granulation technology, the melt granulation technology used for celecoxib operates at 443.15 K, which requires a higher quality heating agent. In classical spherical agglomeration technology, the operation is complicated, and the agglomeration process of celecoxib consumes a large amount of ethanol (good solvent) and cyclohexane (bridging liquid), up to 63.8 g of organic solvent is required for each 1 g of spherical product prepared.…”

“…1b). [20][21][22][23] The traditional granulation technology employs high-cost instruments as well as complex and numerous unit operations. Furthermore, the increase in equipment inevitably leads to increased energy consumption and carbon emission.…”

Design of Single and Multicomponent Drug Spherical Particles with Improved Powder Properties in Water Instead of Organic Solvents: A Case Study of Gemfibrozil

“…Except for the risk of organic residues in products, these solvents are extremely difficult to be degraded in wastewater. 17,18 Besides, the traditional granulation technology, generally including the steps of metering, mixing, granulation, and so on, requires a high-cost apparatus and complex unit operations, further increasing energy consumption and carbon emissions. 19,20 To comply with the trend of sustainable development, the oiling-out spherical agglomeration technology has been developed in our previous work, which could prepare single-or multicomponent spherical particles in water.…”

“…Especially for the spherical agglomeration technology in drug granulation, hazardous organic solvents are widely used in a ternary solvent system. Except for the risk of organic residues in products, these solvents are extremely difficult to be degraded in wastewater. , Besides, the traditional granulation technology, generally including the steps of metering, mixing, granulation, and so on, requires a high-cost apparatus and complex unit operations, further increasing energy consumption and carbon emissions. , To comply with the trend of sustainable development, the oiling-out spherical agglomeration technology has been developed in our previous work, which could prepare single- or multicomponent spherical particles in water. , The technology is based on the oiling-out phenomenon (a special liquid–liquid phase separation), which takes solute-rich oil droplets to produce spherical particles by quenching. , The utilization of water instead of traditional organic solvents is undoubtedly green and environmentally friendly. , Besides, the two-step oiling-out mechanism was developed in our work recently, further expanding the application of this technology for single-component drugs . However, there are still few reports on obtaining multicomponent agglomerates by oiling-out spherical agglomeration technology, and further investigation is needed to the general applicability of this green technology in the pharmaceutical industry.…”

Morphology‐controlled precipitation/remodeling of plate and rod‐shaped hydroxyapatite nanoparticles

“…The control of the morphology of the produced nanoparticles concerns ceramic particles, such as calcium phosphates or calcium carbonate, 24 metallic, 25 polymer, 26 and other particles. Regardless of the process of obtaining particles and their size, control of the morphology and size of individual particles in processes such as crystallization and precipitation remains challenging as it is an instantaneous process 27 . Examples of ways applied to control the size and morphology of nHAp in wet chemical precipitation include changing the synthesis temperature 28 and pH, 29 controlling over addition rate of the reactants, 30 the addition of organic molecules 31 or surfactants (like hexadecyltrimethylammonium bromide or sodium dodecyl sulfate), 32 or addition of the template 33 .…”