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.

Chiral separation of β‐blocker drug nadolol by HPLC – A kinetic and equilibrium study

“…Compared to nadolol separation in the column packed with perphenyl carbamoylated b-CD bonded silica gel conducted in RP, it is interesting to note that the most potent isomer is the last eluted enantiomer in both the cases although the elution order of other components is slightly different [18].…”

Solid‐Liquid Equilibrium of Tröger's Base Enantiomers in Ethanol: Experiments and Modelling

“…An overview of different types of binary mixtures of enantiomers and of their properties in solution can be found in a seminal book [3]. More recently, data about the enantiomers of praziquantel in MeOH [11], those of mandelic acid in water [12], and the enantiomers of propranolol hydrochloride in a mixed MeOH/acetone solvent have been reported [13].…”

Chiral separation using a novel combination of cooling crystallization and a membrane barrier: Resolution of DL-glutamic acid

“…More than fifty percent of approved drugs worldwide are chiral (Li et al, 1999;Wang et al, 2002Wang et al, , 2005. Chirality is a geometric property of nonidentity of an object with its mirror image.…”