title: Solubility, metastable zone width, and racemic characterization of propranolol hydrochloride.
abstract: Characterization of the racemic species, which can be a racemic compound, a racemic conglomerate, or a pseudoracemate (solid solution), is a prerequisite for the design of crystallization resolution processes. It is useful to determine the solid/liquid equilibrium solubility of the enantiomer mixtures for crystallization operation. For the beta-blocker drug propranolol hydrochloride, Gibbs free energy of formation of racemic compound and entropy of mixing of the (R)- and (S)- enantiomers in the liquid state for racemic conglomerate were calculated. The structural differences between (R, S)-propranolol hydrochloride and its (S)-enantiomer were further investigated by powder X-ray diffraction patterns, infrared spectra, and solid-state NMR spectra. The solubility and metastable zone width of (R, S)- propranolol hydrochloride in a mixed solvent of methanol and acetone were determined by cooling crystallization over the temperature range 3.5-42.5 degrees C. The ternary solubility diagram of (R)-, (S)-propranolol hydrochloride was constructed using the same mixed solvent. The diagram will be useful as a guide for choosing crystallization operation conditions to produce pure enantiomers.
authors.affiliation: Department of Chemical and Environmental Engineering, National University of Singapore, Singapore. engp9191@nus.edu.sg
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Wang
authors.forename: Chi Bun
authors.initials: CB
authors.lastname: Ching
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000302:isolation & purification; D003460:Crystallization; D009682:Magnetic Resonance Spectroscopy; D011433:Propranolol / Q000737:chemistry* / Q000302:isolation & purification; D012995:Solubility; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol