Abstract No. 453 In vitro characteristics of imipenem–cilastatin (IPM-CS) particles as embolic agents for geniculate artery embolization: morphology and stability in solution

Abstract

Imipenem–cilastatin (IPM-CS) has been successfully used in particle embolization for osteoarthritis. Information regarding the physical characteristics of IPM-CS particles is lacking. The purpose of this study was to investigate the basic characteristics of IPM-CS particles as embolic agents as well as its optimal conditions. Three samples of 50 mg IPM-CS suspensions were made with contrast in each condition: volume of contrast: 500 μL, 1000 μL; mixing time with vortex mixer: 5s, 10s, 30s. The size of particles was measured using light microscopy. Field of view (FOV) was randomly determined and the size of all visible particles in FOV was measured until the total particle count exceeded 500 in each sample. The particle size distribution in each of the 6 conditions was compared. To investigate time-depend particle changes, 3 samples were made with 50 mg IPM-CS in 1000 μL contrast and a fixed mixture time of 10 s. Particle size was measured immediately, 1 and 3 hours after mixing. The particle size distributions were compared using Kolmogorov-Smirnov test. Over 85% of IPM-CS particles were small in size (0-30 μm) under all preparation conditions. A significant difference in size distribution was seen between 5s-1000μL vs 30s-1000μL groups, primarily in a greater portion of < 10 μm particles with increased mixture time (42.8% vs 47.0% of particle < 10 μm, P = 0.01). Particle size distribution and density in suspension were strongly affected by contrast volume in all the mixture time with 500μL vs 1000μL contrast (61.1-65.5% vs 42.8-47.0% of particles < 10 μm, P < 0.01), suggestive for its soluble feature in contrast. Small, but statistically significant differences in size distributions were observed with elapsed time after mixture. IPM-CS for embolization in osteoarthritis generates particles smaller than 30 μm. IPM-CS particles are relatively stable for mechanical mixture although smaller particles increased with mixture time. The particle size distribution can be affected by both contrast volume and elapsed time. Further understanding of the physicochemical properties of IPM-CS particles may improve optimization for therapeutic delivery.