Agglomeration behavior of anhydrous L-ornithine-L-aspatate crystals during semi-batch drowning-out crystallization

Investigation on the Spherical Crystallization Process of Cefotaxime Sodium

“…Much work has been performed in order to investigate the spherical agglomeration behavior in the process of crystallization, and several mechanisms toward different spherical crystallization processes have been brought forward. − So far, there are two possible methods to obtain the size enlargement of particles during the crystallization step, controlling the minute crystals agglomeration with the goal to obtain spherical agglomerates with controllable properties: (1) spherical agglomeration (SA), which consists of precipitating fine crystals of drug substance then aggregating them using a immiscible liquid (the so-called wetting agent), and (2) quasiemulsion solvent diffusion (QESD), in which a quasiemulsion is formed by droplets of solvent containing the drug and the continuous phase is a liquid in which the drug is immiscible; crystallization occurs inside the droplets because of the counterdiffusion of the solvents through the droplets.…”

“…Recently, crystals of small size (<10 µm) have attracted more and more attention in biomaterial or pharmaceutical industry ascribing to their high bioavailability and dissolution kinetics. 1 However, due to the poor flowability and compressibility and low bulk density of micronized crystals, their downstream processing may be quite difficult, such as filtration, handling, and storage. Therefore, modification and design of micromeritic properties of pharmaceutical powders, such as flowability, packability, and solubility, are necessary to guarantee stable and reliable powder processing.…”

“…Recently, crystals of small size (<10 μm) have attracted more and more attention in biomaterial or pharmaceutical industry ascribing to their high bioavailability and dissolution kinetics . However, due to the poor flowability and compressibility and low bulk density of micronized crystals, their downstream processing may be quite difficult, such as filtration, handling, and storage.…”

“…Following the research of spherical crystallization by Kawashima et al, the spherical crystallization technology has been extensively developed in the pharmaceutical field. − During the processes of the crystallization of lobenzarit disodium, magnesium aspartate, salicylic acid, acetylsalicylic acid, and l -ornithine- l -aspartate, etc., spherical crystallization technology has been successfully employed, and the flowability, compressibility, bulk density, the mean size, and the particle size distribution of the resultant product have been greatly enhanced.…”

Crystallization of RDX by Drowning-Out Combined with Fines Dissolution and Cooling Process

“…However, if the solubility is reasonably high at low temperature, product yield would be quite low. In this case, crystallization by drowning-out in which supersaturation is created by adding an antisolvent is effective to improve the overall yield. − However, despite the high yield, the drowning-out have a troublesome in the control of the level of supersaturation due to extremely high local supersaturation which is primary cause of the generation of very fine crystals …”