USP <729> Emulsion Size Testing
The size of the lipid droplets is critical because larger-size fat globules (>5 µm) can be trapped in the lungs and are also an indicator that the emulsion is destabilizing. The USP <729> test requires two analytical techniques: DLS or laser diffraction to measure the mean and standard deviation of the distribution and light obscuration to measure the large tails >5 µm.
Method I: Mean and standard deviation of the distribution by DLS:
- Test the system with PSL standards at 100, 120, and 400 nm
- The coefficient of variation (COV) must be <10% of the reference values
- Measure the sample, report the intensity-weighted mean, which must be less than 500 nm
Method I is best measured using the Nicomp N3000 system.
Method II: Large-diameter droplet tail (>5 µm) by a single particle optical sizing (SPOS):
- Perform a dilution study to achieve a COV <10% between samples
- Test the sizing and counting accuracy at 5 µm and 10 µm
- The size and count should be within 10% of the certified vales
- Set the lower size limit at 1.8 µm and upper limit at 50 µm
- Vary the measurement time so that there is a factor of two difference >5 µm between two runs
- The volume-weighted result >5 µm (PFAT5) must be <0.05%
Method II is best measured using the AccuSizer APS system.