title: Crystal chemistry of the antibiotic doripenem.
abstract: Doripenem, an ultrabroad spectrum-injectable antibiotic belonging to the wide class of carbapenem beta-lactams, is commonly marketed as powders of a pure monohydrate phase. Here, we have selectively prepared another hydrated phase (a dihydrate) and determined the crystal structure of both forms by state-of-the art powder diffraction methods. Both phases crystallize in the monoclinic P21 space group, and, to some extent, are structurally related. Moreover, by using variable temperature diffractometric analyses, we also discovered a crystalline anhydrous form of doripenem, the structure of which (with two crystallographically independent molecules in the monoclinic P21 space group) remains so far unknown. The thermal interconversion among these phases was further studied by thermogravimetry, differential scanning calorimetry, and thermodiffractometric analyses, and their (metric or stereochemical) mutual relations fully analyzed. The complete structural characterization of the two hydrated phases allows the use of accurate whole pattern profile-fitting procedures for quantitative analyses of these drugs in polycrystalline, or even amorphous, matrices, opening the way to industrial process control and legal protection. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3641-3647, 2014.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Milano 20133, Italy. Electronic address: valentina.colombo@unimi.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Colombo
authors.affiliation: Dipartimento di Scienza ed Alta Tecnologia, Università dell'Insubria, Como 22100, Italy.
authors.forename: Norberto
authors.initials: N
authors.lastname: Masciocchi
authors.affiliation: Dipartimento di Scienza ed Alta Tecnologia, Università dell'Insubria, Como 22100, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palmisano
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D015780:Carbapenems / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D000077726:Doripenem; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D033362:Powder Diffraction; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D014867:Water; D000077726:Doripenem
keywords: X-ray powder diffractometry; crystal structure; hydrates; pseudopolymorphism; thermal analysis