Particle Analysis in Pharmaceutical Applications
Silicone Oil Droplet Detection
Silicone is used as a lubricant on plungers and vial stoppers. It can slough off, or shed, and appear as micro-droplets in a drug formulation. These droplets can also serve as denaturing agents and nucleation centers in bio-pharmaceuticals. Detection of silicone oil droplets in a parenteral particle population is a challenge for obscuration and other traditional methods since they cannot differentiate the droplet from other contaminants.
A parenteral sample contaminated with silicone oil droplets and high particle counts in the USP/EP/JP size ranges of interest was analyzed using by MFI. The LOW magnification setting was used to analyze particles from 2.25 to 300µm at concentrations from 0 to 275,000 particles/ml. High resolution images were stored from 1ml of sample. Each particle within each image frame was automatically measured for: diameter (ECD), area, perimeter, circularity, transparency, maximum Feret’s Diameter , and Aspect Ratio. Using the MFI software, silicone droplets were visually identified and an appropriate software filter, based on intensity and aspect ratio, was created. This filter was then applied to the database representing the complete sample to isolate the silicone droplet sub-population from the total particle population.
Using this morphology-based software filter, 61% of the 676 particles greater than 10µm detected in the contaminated parenteral sample were identified as silicone oil droplets.
