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Marchand, Pierric; Lefebvre, L.; Perez, Guy; Counioux, J.J.; Coquerel, Gérard

doi:10.1023/a:1014964315878

Cited by 6 publications

(3 citation statements)

References 2 publications

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“…Several groups ,− reported another method of determining solubility. Instead of increasing the solubility by increasing the temperature, in this Solvent Addition (SA) method the concentration is decreased by adding solvent (Figure (right)).…”

Section: Introductionmentioning

confidence: 99%

Solubility Determination from Clear Points upon Solvent Addition

Reus

Heijden

Horst

2015

Org. Process Res. Dev.

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A method is described for determining the solubility of multicomponent crystalline compounds from clear points upon sample dilution at a constant temperature. Clear points are established by continuously adding a solvent mixture to a suspension of known composition until a clear solution appears. For validation, this solvent addition method is compared to the traditional equilibrium concentration method at constant temperature and the more recent temperature variation method with which clear point temperatures are determined upon increasing the sample temperature. Solubility data of binary systems (1 solute, 1 solvent) measured using the solvent addition method are obtained relatively quickly compared to the equilibrium concentration method. These solubility data are consistent with those of the temperature variation and the equilibrium concentration method. For the temperature variation method, the results are dependent on the heating rate. Likewise, for the solvent addition method, they are dependent on the addition rate. Additionally, for ternary systems involving antisolvent or cocrystals, solubilities are determined at a constant temperature using the solvent addition method. The use of the solvent addition method is especially valuable in the case of solvent mixtures and other complex multicomponent systems, in which the temperature variation method cannot be applied easily. ■ INTRODUCTIONIn production often a crystallization step is required for purification and final crystalline particulate product formation. 1,2 The solubility or phase diagram of such compounds is essential information for efficient and reliable crystallization process design and operation. 3−6 The phase diagram indicates the most stable phases at specific compositional and temperature conditions, 1,4−6 determines the achievable yield, 7 and enables the monitoring of the supersaturation during the crystallization process. 7,8 Traditionally the solubility is measured through equilibration of a suspension. 1 The solubility is then equal to the concentration in the equilibrated solution, which can be sampled and determined by, for example, a gravimetric method or HPLC (Figure 1 (left)). Although the Equilibrium Concentration (EqC) method is widely accepted and considered accurate, 1 it is laborious and time-consuming. Currently, commercial equipment from various suppliers is available that streamlines measurements through a temperature variation (TV) method in which clear points are measured. 9−11 In the TV method the solubility is changed by changing the temperature, until it matches the concentration. A clear point is then the temperature at which, upon increasing the temperature, a suspension turns into a clear solution. Figure 1 (center) shows the principle of a clear point measurement using the TV method. If the heating rate is sufficiently small, the crystal dissolution rate is fast and the clear point can be assumed to be equal to the saturation temperature. 10 This TV method is much less labor intensive, is much faster, and allows f...

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Section: Introductionmentioning

confidence: 99%

Solubility Determination from Clear Points upon Solvent Addition

Reus

Heijden

Horst

2015

Org. Process Res. Dev.

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“…An isothermal section ( T = 30 °C) of the ternary phase diagram [(+)-imeglimin-2,4-dichlorophenylacetate/(−)-imeglimin-2,4-dichlorophenylacetate/methanol] is presented in Figure . The boundaries of the stable domains were determined by means of discontinuous isoperibolic thermal analysis (DITA) measurements . The upper points belong to the solubility curves, whereas the points that are lined up belong to the tie-lines that limit the two-phase domains and the three-phase domain.…”

Section: Introductionmentioning

confidence: 99%

Resolution of (±)-Imeglimin-2,4-dichlorophenylacetate Methanol Solvate by Preferential Crystallization

Wacharine-Antar

Levilain

Dupray

et al. 2010

Org. Process Res. Dev.

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The resolution of this derivative was optimized at 2-L scale in methanol by using two preferential crystallization modes (auto-seeded polythermic programmed preferential crystallization, hereafter AS3PC, and seeded isothermal preferential crystallization, hereafter SIPC) and by tuning the starting temperature. The results evidenced that the AS3PC mode is more efficient than the SIPC mode, and the higher the starting temperature, the higher the productivity. Despite a careful tuning of the operating conditions and a stable conglomerate offering a full chiral discrimination in the solid state, the enantiomeric excess of the crude solid obtained by preferential crystallization remained lower than 90%. However, this can be improved up to 99% by a single recrystallization of the methanol solvate of the imeglimin-2,4-dichlorophenylacetate since it crystallizes as a stable conglomerate without any detectable partial solid solution.

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“…[6][7][8][9] for details on the experimental conditions). This technique is of particular interest when solid phases are efflorescent as in the present study.…”

Section: Ditamentioning

confidence: 99%

Study of solid-liquid and solid-vapour equilibria in tenatoprazole potassium salt/solvents systems

Tauvel

Cartigny

Sanselme

et al. 2011

XXXVII JEEP – 37th Conference on Phase Equilibria

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Abstract. Tenatoprazole, 5-methoxy-2-{[(4-methoxy-3,5-dimethyl-2-pyridyl)-methyl]-sulfinyl}-imidazo-[4,5-b]-pyridine, is a proton pump inhibitors (PPI). A conglomerate screening of (±) tenatoprazole by crystallisation of various salts and solvates led to the detection of potassium salts dihydrate and efflorescent ethanol and methanol solvates giving a full chiral discrimination in the solid state. The aim of this study was to determine solid-liquid and solid-vapour equilibria of the system [tenatoprazole potassium salt / methanol / ethanol] by combining structural, thermal and dynamic sorption / desorption data. The isothermal section at 20°C of this system was determined by using DITA (Discontinuous Isoperibolic Thermal Analysis) measurements and structural studies (in situ XRPD). Despite extensive structural similarities the study performed here suggests the existence of a partial solid solution between methanol and ethanol solvates.

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Cited by 6 publications

References 2 publications

Solubility Determination from Clear Points upon Solvent Addition

Solubility Determination from Clear Points upon Solvent Addition

Resolution of (±)-Imeglimin-2,4-dichlorophenylacetate Methanol Solvate by Preferential Crystallization

Study of solid-liquid and solid-vapour equilibria in tenatoprazole potassium salt/solvents systems

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