Physico-chemical characterization of a novel tricyclic beta-lactam antibiotic.
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.
Marini
A
A
CSGI, Dipartimento di Chimica Fisica, Università degli Studi di Pavia, Viale Taramelli 16, 27100 Pavia, Italy. marini@matsci.unipv.it
Berbenni
V
V
Bruni
G
G
Sinistri
C
C
Maggioni
A
A
Orlandi
A
A
Villa
M
M
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007769:Lactams; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D011208:Powders; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013816:Thermodynamics; D014961:X-Ray Diffraction; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D007769:Lactams; D011208:Powders; D047090:beta-Lactams; C104757:sanfetrinem