Physico‐chemical Characterization of a Novel Tricyclic β‐Lactam Antibiotic

Abstract

GV118819X, a novel tricyclic β‐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. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 232–240, 2000