Objective: To provide recommendations for crystal form consistency evaluation of cephalosporin injections by comparing the crystal form of cefotaxime sodium between its generic raw material or preparation and refe-rence medical product by several popular polymorph methods. Methods: According to the physical and chemical properties of cefotaxime sodium, methods including powder X-ray diffraction(CuKα radiation: λ=1.541 862 Å; voltage: 45 kV; current: 200 mA; scan scope: 3-60 °), thermal analysis(scan scope: 30-400 ℃; heating rate: 10 ℃·min-1), Raman mapping(excitation wavelength: 785 nm; mapping scope: 1 mm×1 mm) and scanning electron microscope(voltage: 5.0 kV; magnification: ×400~×1 200; detector: secondary electron), were selected to evaluate crystalline characteristics. Results: The crystal structure of all the generic batches was basically the same as that of reference preparation, and their characteristic temperatures of desolvation (77 ℃) and thermal decomposition (208 ℃) were close to each other. However, only reference preparation had a volatilization peak of low boiling solvent near 54 ℃ in the thermogravimetric line, and contained a small amount of variant crystals. The crystals of generic batches were flaky with small particle size (several microns), while those of reference preparation were spherical with large particle size (close to 100 μm). Conclusion: The evaluation of crystal form consistency for cephalosporin injections can be comprehensively characterized by the above methods, obtaining the crystal structure, the situation of crystallized water and solvent, polymorphic phenomenon, and the difference of crystal habit.
QI Shu-ye, ZOU Wen-bo, YAO Shang-chen, XU Ming-zhe, YIN Li-hui
. Discussion on polymorph consistency evaluation for cefotaxime sodium for injection*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(10)
: 1836
-1843
.
DOI: 10.16155/j.0254-1793.2021.10.22
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