Flow Microscopy for Parenteral Particles
11 June 2007
Particles in parenteral formulations can now be counted and measured at a speed and with an efficiency which renders current techniques obsolete. Micro flow technology even allows the analysis of formulation components, contaminants and manufacturing artifacts enabling a safer and more consistent gauge of product acceptability.
Particle detection and measurement in parenterals has been extensively investigated. USP General Chapter 788 specifies light obscuration and microscopy as the methods for counting and sizing particles. However, both techniques have limitations.
Light blockage under-sizes and under-counts non-spherical and translucent particles. Microscopy is time-consuming, tedious and operator-dependent. Image analysis has been previously investigated as a means to improve the efficiency of the manual microscopic method. Doubts have been raised as to the ability of image analysis systems to capture the smallest product particles, and to provide a comprehensive analysis of a sample.
Flow microscopy, the technique utilized by Brightwell Technologies MFI™ delivers the instrumental benefits (consistency, reliability and speed) of light blockage methods alongside the precision, sensitivity and additional information (size, shape and image) of manual microscopy.
Protein formulations present a significant challenge to particle detection and measurement. Particles formed by protein aggregation are:
- Translucent.
- Irregular sizes and shapes.
- Fragile and easily deformed.
- Present in very low concentrations.
Particles with these characteristics cannot be reliably detected and measured by light obscuration.
In the Brightwell Technologies system the sample is drawn through a precision flow cell. A range of delivery options ensures that the sample is delivered with the least possible damage to fragile particles. Images are acquired many times each second and all particles in frame are detected and measured.
Results are presented as concentration versus size histograms. Multidimensional size data is recorded which allows morphological analysis of particles. Real time data processing enables continuous sampling and trend charting, while particle images can be simultaneously viewed to allow confirmation of the nature of particles.
Dave Thomas of Brightwell Technologies reports, "Flow microscopy typically detects ten times as many particles in a parenteral solution compared to a light obscuration technique. The technology is highly effective in addressing the challenges encountered upon measuring very low concentrations of broadly heterogeneous particles. When you consider that, in addition, we can individually view each particle and segregate particle populations based on a multitude of morphological parameters, you see the benefit of the system."
