Solubility and Some Crystallization Properties of Conglomerate Forming Chiral Drug Guaifenesin in Water

Resolution of Racemic Guaifenesin Applying a Coupled Preferential Crystallization-Selective Dissolution Process: Rational Process Development

“…The solubilities of both the racemic mixture and the pure enantiomer show a strong nonideal and nonlinear behavior, rather two lines with a bend in between, indicating a potential phase change. However, during this study (ref ( 10 )), only the known polymorph was found and hydrate formation was not detected. Though, the occurrence of a second liquid phase, i.e., a stable or metastable liquid–liquid demixing, was indicated.…”

“…Guaifenesin dissolved in water is known to form a conglomerate 10 without occurrence of solvates or other polymorphs over the temperature and composition range of interest. It crystallizes in an orthorhombic crystal lattice 11 (space group P 2 1 2 1 2 1 ) with a needle-like habit of the macroscopic particles ( Figure 3 a).…”

“… (a) Microscopic image of pure ( R )-guaifenesin after recrystallization. (b) Solubility of racemic (black and red squares) and ( R )-guaifenesin (blue squares) taken from ref ( 10 ) in water in comparison to the ideal solubility curve calculated according to Schröder–van Laar (black solid line). Dashed lines are just guides for the eye.…”

“…Solubility data of the racemic mixture and the ( R )-enantiomer measured with a polythermal method 10 and utilized for the design of the first experiment are shown in Figure 3 b. The solubilities of both the racemic mixture and the pure enantiomer show a strong nonideal and nonlinear behavior, rather two lines with a bend in between, indicating a potential phase change.…”

“…Guaifenesin, on the contrary, forms a stable conglomerate in water, and a procedure to access the pure enantiomers batchwise from enriched and racemic solutions was already reported. 6 , 10 …”