Experimental investigation and prediction of oiling out during crystallization process

Predicting the Solubility Advantage of Amorphous Pharmaceuticals: A Novel Thermodynamic Approach

“…[21][22][23] The solubility line represents the concentration of the API in the solvent-rich phase which is in equilibrium with the pure crystalline API. This concentration is the solubility of the crystalline API ‫ݔ‬ ூ ሺሻ which is obtained by calculating the solid-liquid equilibrium (SLE) 24 of the API.…”

“…[21][22][23][25][26][27] In systems where a polymer acts as the solvent and crystallization is hindered due to high viscosity, the liquidliquid demixing is even more often observed and usually called "amorphous demixing". Tian et al 28 investigated the thermodynamic phase behavior of felodipine in Soluplus and in hydroxypropyl methylcellulose acetate succinate and postulated an amorphous demixing in these sytems.…”

Phase equilibrium and mechanisms of crystallization in liquid–liquid phase separating system

“…Time for nucleation with 95% confidence interval and relative distance to the saturation of droplets solutions (Sols. [1][2][3][4][5][6][7][8][9][10][11][12] with 90-35% ethanol in solvents. Solid dots: average nucleation time of droplet solutions with 95% confidence interval.…”

“…Binary solvent mixtures are commonly used in industrial crystallizations and recently more research on more complex multiphase crystallization processes with liquid-liquid phase separation (LLPS) have been reported. Liquid-liquid equilibrium data have been investigated for some "anti-solvent" crystallization experiments [2,3], spherical crystallizations using a three solvents system [4,5], oiling out phenomena [6][7][8][9][10] and reverse addition processes [11]. The LLPS makes crystallization difficult in protein systems [12,13], prevents drug nucleation [14][15][16], and hinders nucleation in crystallization of droplets [17].…”

A method to crystallize substances that oil out

“…Using simultaneous measurements of solute concentration and turbidity, Groen and Robert (2001) found that concentrated micro-droplets form first in a continuous phase of lower concentration followed by nucleation at the interface of the droplets-continuous phase. Lastly, it is worth mentioning that modelling was not extensively used to predict the eventual occurrence of LLPS in the case of crystallization until recently as reported by Kiesow et al (2008), for the crystallization of 4,4 -dihydroxydiphenylsulfone.…”