Evaluation of particle size distribution of sub-visible particles in powder injections with different packaging forms - small-sized sub-visible particles should not be ignored.

Abstract

Objectives: Sub-visible particle, or particulate matter, is an important indicator in the safety assessment of clinical infusions. The present study aims to evaluate the effect of the packaging formats of antibiotic on the distribution of sub-visible particles in the small particle size range (<10 μm), to provide evidence for explanation to clinical adverse reactions and guidelines for rational drug use.

Methods: The conventional light blockage and the single particle optical sensing (SPOS) technology were applied to determine the size distribution of the sub-visible particles in the redissolved injections in different packages (dual-chamber bag and vial) from different manufacturers. In order to verify our hypothesis, the influences of active pharmaceutical ingredient (API) and solvent were controlled. Further, scanning electron microscopy (SEM) was utilized to observe the morphological characteristics of sub-visible particles from different package injections.

Results: After redissolving, the small-sized sub-visible particles (<10 μm) in the solution of injectable powder packaged in the dual-chamber bag were significantly lower than that of the conventional injectable powder packaged in the vial, and the difference remained significant after controlling for API. The results observed by SEM also supported the differences in the amount of particulate matter between the two packaging formats, showing a higher number of sub-visible particles from sodium chloride dissolved preparations packed in vails, with irregular shapes.

Conclusion: In our study, the differences in the distribution of sub-visible particles were mainly attributed to the packaging formats. The dual-chamber bag injection might be an effective alternative to reduce the adverse reactions caused by sub-visible particles.