PROCESSING EFFECTS ON CRYSTALLINITY OF CEPHALEXIN - CHARACTERIZATION BY VACUUM MICROBALANCE

Cephalexin is known to exist in several pseudopolymorphic or solvated forms, and to be slowly hydrolysed by water, and accordingly the study of its interaction with water is particularly important. Three common processing techniques - milling, spray drying and freeze drying - are examined for their influence on the interactions with water, which are probed by measuring the water sorption isotherms on a vacuum microbalance. In addition, water sorption isosteres are determined directly to quantify the sorption heats as a function of moisture content. Crystalline cephalexin shows discreet formation of mono and dihydrated forms, and their formation is easily reversible, indicating that water plays little part in the stabilisation of the lattice. Spray and freeze drying both lead to a form of cephalexin which continuously sorbs water without formation of a stoichiometric hydrate, and does not reversibly dehydrate; this indicates the sample is highly disordered and that the water can access a wide range of lattice sites which play a significant part in the overall solid state stability. Ball-milled samples are intermediate, with a partially discreet monohydrate formation as the vapour pressure is raised, which is partially reversible as the pressure is reduced. The increased disorder over the crystalline sample allows more sites to become accessible to the water samples.