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 diastereoisome rs, only A is available as a pure compound. By analyzing mixtures of GV1188 19X and A, a partial phase diagram is constructed, which indicates the pres ence of a eutectic when the A fraction is similar to 39%. Moreover, the mel ting enthalpies of the eutectic mixture and of diastereoisomer B can be est imated. With the exception of the pure A form, all mixtures undergo importa nt modifications in morphology and microstructure as a consequence of therm al treatments, which induce melting/amorphization of the eutectic, and crys tallization of the A form. Analyses of the sieved fractions of GV118819X de monstrate that it consists of acicular crystals of different composition, w ith the larger crystals having a larger A fraction than the smaller ones. G rinding causes melting/amorphization of the eutectic and, following hours-l ong treatments, the formation of a substantial fraction of submicron partic les with unusually low melting temperatures. (C) 2000 Wiley-Liss, Inc.