In situ monitoring, control and optimization of a liquid–liquid phase separation crystallization

Process Design for Antisolvent Crystallization of Erythromycin Ethylsuccinate in Oiling-out System

“…The oiling out phenomenon was first reported in a protein system 9 and was found to be similar to the phase behavior of polycyclic aromatic hydrocarbons system 10 . Because oil droplets formed before nucleation and traditional methods lack effectively process control on crystallization, consequentially impurity is incorporated into the final products 11 . Although the oiling out phenomenon has been utilized to change the characteristics of crystals in a few studies in recent years [12][13][14][15] , the main purpose of crystallization is still purification.…”

Enhancements and Limits in Drug Membrane Transport Using Supersaturated Solutions of Poorly Water Soluble Drugs

“…Highly supersaturated solutions will undergo LLPS when a certain threshold concentration is exceeded whereby a homogeneous one‐phase system separates into two liquid phases. LLPS is also referred to as oiling‐out or liquid–liquid demixing . LLPS has been widely observed in a variety of systems including polymer blends, proteins, metals, and is often prevalent, albeit undesired, during industrial crystallization .…”

“…LLPS is also referred to as oiling‐out or liquid–liquid demixing . LLPS has been widely observed in a variety of systems including polymer blends, proteins, metals, and is often prevalent, albeit undesired, during industrial crystallization . Svärd et al reported LLPS for the water–vanillin system.…”

Change in glycine polymorphs induced by minute-bubble injection during antisolvent crystallisation

“…Examination of glycine solubility is essential to realise supersaturation in the bulk solution and to surmise the generation of local supersaturation in the regions around the minute gas-liquid interfaces during antisolvent crystallisation. Hence, the time change in the concentration of dissolved glycine was measured when commercial-grade glycine was added in excess to a methanol-water solution at various V MeOH values, with T s maintained at 303 K. The steady state level of the dissolved glycine concentration was defined as the solubility of glycine (C S ) at a specified V MeOH value, as suggested by Duffy et al [19] and Zhou et al [20], and the supersaturation ratio of glycine in the bulk solution (C/C S ) was calculated from C S and C immediately after the rapid addition of methanol or the saturated glycine solution. The obtained values of C S , C/C S , and C were plotted against V MeOH , as shown in Fig.…”