Pharmaceutical Particle Analysis
Air Bubble Identification & Quantification
Bubbles can be introduced in pharmaceutical formulations as a result of handling or manufacturing processes. This is particularly the case with reconstituted lyophilized products. Regardless of how they are created, it is desireable to eliminate bubbles wherever possible (using sonication or other degassing techniques). However, it may be impractical or impossible to completely remove them. The remaining bubbles will then interfere with particle measurements since they cannot be reliably distinguished from real particles using conventional techniques such as obscuration. The result is unreliable results which may indicate a higher number of particles in various size ranges than actually exist.
MFI uses morphology-based software filters to identify and quantify bubbles. An experiment was performed to illustrate this feature using a sample with high particle counts in the USP/EP/JP size ranges of interest (as measured by obscuration). Using the MFI software, bubbles were visually identified and an appropriate software filter, based on circularity, was created. This filter was then applied to the database representing the complete sample to isolate single bubbles from the total particle population.
A subsequent inspection of the filtered database revealed the presence of bubble clusters (coalescent air bubbles). A new software filter, based on intensity/aspect ratio, was created and applied to the remaining images to isolate these clusters.
Using the morphology-based software filters, 98% of the 3796 particles/ml detected in the original sample were identified as air bubbles or bubble clusters with an error rate of 0.05%.
