title: Solubility and some crystallization properties of conglomerate forming chiral drug guaifenesin in water.
abstract: The solubility of 3-(2-methoxyphenoxy)-propane-1,2-diol, the well-known chiral drug guaifenesin 1, in water has been investigated by means of polythermal and isothermal approaches. It was found that the solubilities of racemic and enantiomeric diols rac- and (R)-1 depend strongly on temperature. The ternary phase diagram of the guaifenesin enantiomers in water in the temperature range between 10°C and 40°C was constructed. Clear evidence was obtained that rac-1 crystallizes as a stable conglomerate. The Meyerhoffer coefficient for the guaifenesin-water system is more than two and strongly depends on temperature. Neither crystalline hydrates nor polymorphs were detected within the range of conditions covered. Metastable zone width data with regard to primary nucleation were also collected for rac-1 and (R)-1. On the basis of the knowledge acquired, the resolution of racemic guaifenesin by preferential crystallization from solution could be realized successfully.
authors.affiliation: A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088, Russian Federation.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Fayzullin
authors.forename: Heike
authors.initials: H
authors.lastname: Lorenz
authors.forename: Zemfira A
authors.initials: ZA
authors.lastname: Bredikhina
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Bredikhin
authors.forename: Andreas
authors.initials: A
authors.lastname: Seidel-Morgenstern
mesh_terms: D003460:Crystallization; D005100:Expectorants / Q000737:chemistry*; D006140:Guaifenesin / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D005100:Expectorants; D014867:Water; D006140:Guaifenesin
keywords: X-ray powder diffractometry; chirality; guaifenesin; metastable zone width; miscibility gap; phase diagram; preferential crystallization; racemic conglomerate; separation science; solubility