Cleanliness of any fluid, but in particular those put into the human circulatory system, can be of paramount importance. In the case of these fluids, any particulates must be small enough to easily pass through the circulatory system, and be processed and released as waste, in addition to being non-toxic. Stringent regulatory requirements already exist for both visible (>100 µm) and sub-visible (1-100 µm) particulates in parenteral liquids. Filters are often used to clean up excessive particle populations, but how well do these work?
As reliable measurement techniques for nanometer (<100 nm) and sub-micron (100-1,000 nm) particles become available, we can expect closer scrutiny of these particulate size ranges as well. While the current focus is on particulates in drug formulations, parenteral fluids such as IV saline also need to be monitored.
Spectradyne's innovative nCS1TM nanoparticle analyzer is ideally suited for accurate quantification of these particulates. To demonstrate the efficacy of the nCS1 in this application, two sources of 0.9% saline were compared for particulate content. One source was an IV bag, the second was a pre-filled flush syringe.
The figure to the right shows the results for two size ranges of nanoparticles, 75-400 nm and 250-1600 nm (inset). The results clearly show that the saline in the pre-filled flush syringe (green) is cleaner than the bagged IV saline (blue). These measurements highlight the broad size range of the nCS1 (in this case 75-2,000 nm) over a concentration range of nearly six orders of magnitude.
The table below also summarizes the absolute concentration results for two different ranges:
In a related study, the effect of filtering a nanomedicine component was recorded using the high resolution of the nCS1.
A sample containing a broad distribution of ferromagnetic particles used for cell isolation was analyzed before and after filtration through a cellulose acetate membrane with a 0.45 µm nominal pore size. As a positive control, 794 nm polystyrene beads were added to both samples at a final concentration of 2×107 particles/ml (the control was added to the filtered sample after filtration).
The results of the filter study are shown at right, with the unfiltered sample in blue and the filtered one in green. A surprising outcome is that the filter removes a significant number of particles well below its rated size of 0.45 µm. In addition, the filter showed relatively poor particle rejection in the 450-750 nm size range, reducing the particle concentration by only a factor of about 3. This indicates relatively poor filter performance versus what might be expected.