Physico-chemical characterization of a novel tricyclic beta-lactam antibiotic. 2000

A Marini, and V Berbenni, and G Bruni, and C Sinistri, and A Maggioni, and A Orlandi, and M Villa
CSGI, Dipartimento di Chimica Fisica, Università degli Studi di Pavia, Viale Taramelli 16, 27100 Pavia, Italy. marini@matsci.unipv.it

GV118819X, a novel tricyclic beta-lactam antibiotic of GlaxoWellcome, is a racemic mixture of two diastereoisomers, A and B. Of the two diastereoisomers, only A is available as a pure compound. By analyzing mixtures of GV118819X and A, a partial phase diagram is constructed, which indicates the presence of a eutectic when the A fraction is approximately 39%. Moreover, the melting enthalpies of the eutectic mixture and of diastereoisomer B can be estimated. With the exception of the pure A form, all mixtures undergo important modifications in morphology and microstructure as a consequence of thermal treatments, which induce melting/amorphization of the eutectic, and crystallization of the A form. Analyses of the sieved fractions of GV118819X demonstrate that it consists of acicular crystals of different composition, with the larger crystals having a larger A fraction than the smaller ones. Grinding causes melting/amorphization of the eutectic and, following hours-long treatments, the formation of a substantial fraction of submicron particles with unusually low melting temperatures.

UI MeSH Term Description Entries
D007769 Lactams Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams. Lactam,Lactim,Lactims
D008855 Microscopy, Electron, Scanning Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY. Scanning Electron Microscopy,Electron Scanning Microscopy,Electron Microscopies, Scanning,Electron Microscopy, Scanning,Electron Scanning Microscopies,Microscopies, Electron Scanning,Microscopies, Scanning Electron,Microscopy, Electron Scanning,Microscopy, Scanning Electron,Scanning Electron Microscopies,Scanning Microscopies, Electron,Scanning Microscopy, Electron
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D011208 Powders Substances made up of an aggregation of small particles, as that obtained by grinding or trituration of a solid drug. In pharmacy it is a form in which substances are administered. (From Dorland, 28th ed) Powder
D002152 Calorimetry, Differential Scanning Differential thermal analysis in which the sample compartment of the apparatus is a differential calorimeter, allowing an exact measure of the heat of transition independent of the specific heat, thermal conductivity, and other variables of the sample. Differential Thermal Analysis, Calorimetric,Calorimetric Differential Thermal Analysis,Differential Scanning Calorimetry,Scanning Calorimetry, Differential
D002627 Chemistry, Physical The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes. Physical Chemistry,Chemistries, Physical,Physical Chemistries
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D014961 X-Ray Diffraction The scattering of x-rays by matter, especially crystals, with accompanying variation in intensity due to interference effects. Analysis of the crystal structure of materials is performed by passing x-rays through them and registering the diffraction image of the rays (CRYSTALLOGRAPHY, X-RAY). (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Xray Diffraction,Diffraction, X-Ray,Diffraction, Xray,Diffractions, X-Ray,Diffractions, Xray,X Ray Diffraction,X-Ray Diffractions,Xray Diffractions

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