Physico-chemical characterization of a novel tricyclic β-lactam antibiotic

✍ Scribed by A. Marini; V. Berbenni; G. Bruni; C. Sinistri; A. Maggioni; A. Orlandi; M. Villa

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 276 KB
• Volume: 89
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/(sici)1520-6017(200002)89:2<232::aid-jps10>3.0.co;2-5

✦ Synopsis

GV118819X, a novel tricyclic ␤-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 ∼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.