Compressed pellet X-ray diffraction monitoring for optimization of crystallinity in lyophilized solids: imipenem: cilastatin sodium case.

A rapid, quantitative X-ray diffraction method to monitor the relative degree of crystallinity of lyophilized materials is described. The method was applied to determine the degree of crystallinity of imipenem [(5 R, 6 S)-3-[[2(formimidoylamino)ethyl]thio]-6-[(R)-1- hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid] in 60 process related samples of the combination product of imipenem and amorphous cilastatin sodium (sodium (Z)-7-[[(R)-2-amino-2-carboxyethyl]thio]-2-[(S)-2,2- dimethylcyclopropanecarboxamido]-2-heptenoate). This assured optimizing process conditions which affect the improvement of crystallinity.