Ternary Solubility Phase Diagrams of Mandelic Acid and N-Methylephedrine in Chiral Solvents with Different Carbon Chain Lengths

Abstract

Ternary solubility phase diagrams of mandelic acid and N-methylephedrine species in chiral solvents, (S)-methyl lactate, (S)-propyl lactate, and (S)-butyl lactate, have been determined. Solubility measurements were performed for enantiomeric compositions ranging from 50:50 mixtures to the pure enantiomers and temperatures ranging from 0 to 35 °C for mandelic acid and from 0 to 25 °C for N-methylephedrine, respectively. The ternary solubility phase diagrams of mandelic acid and N-methylephedrine showed symmetric behavior. It became obvious that increasing chain length of chiral solvents, i.e. from (S)-methyl lactate to (S)-butyl lactate, resulted in decreasing solubility. 1HNMR and Raman spectroscopy have been applied to characterize the solute-solvent interaction in the liquid phase for mandelic acid system. Molecular modeling calculations were performed for mandelic acid to get a deeper understanding of the solute−solvent interactions. The effect of the solvent on the shape of the solubility isotherms is discussed by determining the relative solubility ratios (αmol-values) just for N-methylephedrine.

Cooling Crystallization of Indomethacin: Effect of Supersaturation, Temperature, and Seeding on Polymorphism and Crystal Size Distribution

“…33 Several other studies describes the importance of non-covalent solute-solvent interactions influencing the outcome of crystallization processes. [34][35][36][37][38][39] In case of IMC nucleation, specifically α-IMC, three hydrogen bonded molecules of IMC needs to orient to form an asymmetric unit of crystal structure as shown in Fig. 1.…”

Solubility of tridecanedioic acid in pure solvent systems: An experimental and computational study

“…The solubility study of crystalline solids in pure solvent and/or mixed solvent systems is a major interest of research for both engineering and pharmaceutical researchers due to its implication on purification [2,3], process control and design [4,5], and pharmaceutical dosage design [6]. In the thermodynamic theory of (solid + liquid) equilibria (SLE), solubility is related with fusion enthalpy, fusion temperature, actual temperature, and activity coefficient [7].…”

“…In addition, with the aid of quantum mechanics calculations, several studies on the solubility behaviour of organic crystalline solids in different solvents explored the role of (solute + solvent) interaction and the link of such interaction with solubility. Tulashie et al [3] illustrated the effect of chain length of the chiral solvents on mandelic acid solubility with the (solute + solvent) interaction energy computed from VAMP calculations. The higher solubility of levofloxacin in acetic acid than in other five solvents was rationalized by Zhang et al [24], too using (solute + solvent) interaction energy obtained from DFT calculations.…”

Verfahren zur Enantiomerentrennung

“…0.3) gemessene eutektische Zusammensetzung [160] bleibt in Gegenwart beider beteiligten Lçsungsmittel unverändert. Selbst bei Verwendung des chiralen Lçsungsmittels DET (sowie weiteren optisch aktiven Lçsungsmitteln, wie Lactaten) [137] wird keine nennenswerte Asymmetrie im MAPhasendiagramm induziert, die für Trennzwecke genutzt werden kçnnte. In beiden gezeigten Lçsungsmitteln steigt die Lçslichkeit der Mandelsäurespezies mit der Temperatur und ist für die racemische Verbindung hçher als für die Enantiomere.…”