title: Precipitation of calcium gluceptate from aqueous solutions.
abstract: A precipitate encountered in solutions of calcium gluceptate was identified as hydrated calcium gluceptate. Precipitation was associated with a change from a very soluble amorphous anhydrous form to a sparingly soluble crystalline hydrate, the presence of seed crystals inducing crystallization, and unsuitable proportions of the alpha- and beta-epimers of calcium gluceptate. Various commercial samples and the corresponding precipitates were examined by elemental analysis, thermal analysis, X-ray diffraction, IR spectroscopy, and GC-MS. The proportion of the alpha- and beta-epimers in commercial samples was quantitated by GC. In this method, an aqueous solution of calcium gluceptate was converted into a mixture of glucoheptonic acids and their corresponding lactones by passage through a cation-exchange resin. The solution was freeze-dried, the acid-lactone mixture converted to the gamma-lactones using concentrated hydrochloric acid, and the resulting material trimethylsilylated with trimethylsilylimidazole. Stability studies of solutions prepared from calcium gluceptate obtained from various commercial sources indicate that above approximately 50% alpha-epimer, stability decreased with an increase in the relative proportion of the alpha-epimer. Material complying with USP specifications (pure alpha-epimer) is the least stable in solution. It is suggested that calcium gluceptate containing approximately equal proportions of the alpha- and beta-epimers be introduced in the USP monograph together with a method for estimating the proportions of the epimers.
mesh_terms: D055598:Chemical Phenomena; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D012995:Solubility; D012996:Solutions; D013237:Stereoisomerism; D013400:Sugar Acids / Q000302:isolation & purification*; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D012996:Solutions; D013400:Sugar Acids; C007852:alpha-glucoheptonic acid