Abstract

Purpose: Different marketed samples of cefuroxime sodium for injection, reconstituted under similar conditions, exhibited differences in reconstitution time. The contribution of variables like the solid form, particle size distribution, hygroscopicity, moisture content and wettability towards variations in the reconstitution time of cefuroxime sodium for injection was assessed. Methods: All samples of cefuroxime sodium for injection were reconstituted by the manual inversion method. Solid form characterization was carried out by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, hot stage microscopy (HSM), and thermo-gravimetric analysis (TGA). The particle size distribution was measured by laser diffraction and the hygroscopicity and moisture content were determined by the dynamic vapor sorption (DVS) technique and Karl Fischer titration respectively. Wettability was measured by contact angle determination using the capillary rise method. Results: No differences were detected in the solid form of the marketed samples. Within the same sample, the particle size distribution exhibited a parabolic correlation with reconstitution. Across different samples, there existed an inverse rank correlation between reconstitution and particle size (D₉₀). The hygroscopicity and moisture content had a significant effect on the reconstitution time of different samples. An almost linear correlation was observed between wettability and reconstitution times of various samples. Conclusion: Complete reconstitution prior to administration, an important pharmacopoeial prerequisite, is affected by a variety of parameters which need to be carefully controlled. In the case of selected samples of cefuroxime sodium powder for injection, the particle size distribution, hygroscopicity, moisture content, wettability had a significant effect on reconstitution time; however, the solid state form did not affect the reconstitution time.


Keywords:  Reconstitution time   Powder for injection   Cefuroxime sodium