Estimation of the degree of crystallinity of cefazolin sodium by X-ray and infrared methods.

Abstract

The pentahydrate (alpha form) of cefazolin sodium (CEZ) exhibited sharp X-ray diffraction peaks, while the dehydrated alpha form showed weak but distinct diffraction peaks. As expected the amorphous form exhibited a diffuse and halo diffraction pattern. The X-ray procedure to estimate the degree of crystallinity of CEZ was based upon the measurement of the total scattering and the scattering from the crystalline region of the drug. The major difference in the infrared (IR) spectra among the three forms of CEZ was the absence of a spectral band at 1542 cm-1 in the amorphous form. The IR procedure was based upon the measurement of the peak percentage area ratio between the bands at 1542 and 1760 cm-1, where the latter was used as a normalizing peak. The degree of crystallinity of CEZ samples, obtained by either freeze-drying aqueous CEZ solutions or storing the crystalline forms under different humidity conditions, was determined by these two methods. Although the correlation of results by the two methods was good, the X-ray procedure appears to be superior since it can differentiate among the three solid CEZ forms, whereas IR could distinguish between only crystalline and amorphous CEZ, reproducibly.