USP <729> In Practice: Reliable Measurement of Lipid Injectable Emulsions with Litesizer DLS and Litesizer DIF
USP <729> requires the testing of mean droplet diameter (MDD) in lipid injectable emulsions. We measured a 10 % lipid emulsion by 2 different methods. Dynamic light scattering (DLS) returned a MDD of ~180 nm for dilutions of 0.3 to 5 drops per mL saline (RSD < 1.5 %). Laser diffraction yielded D50 of ~180 nm when loading 5 to 15 drops into the water-filled tank (RSD < 1.2 %). Both methods proved simple, robust, and repeatable for USP <729> testing.
The United States Pharmacopeia (USP) chapter <729> Globule Size Distribution in Lipid Injectable Emulsions (1) defines two criteria to ensure the safety and quality of lipid-based parenteral drugs. The first is the mean droplet diameter (MDD), which must not exceed 500 nm. The second is the percentage of fat globules larger than 5 μm (PFAT5), which must remain below 0.05%. While PFAT5 determination requires particle-counting methods such as light obscuration or microscopy, distribution-based analyzers using dynamic light scattering (DLS) and laser diffraction (LD) can deliver detailed information on globule size across the submicron to low-micron range. These techniques are therefore ideally suited for assessing MDD as defined in USP <729>.
Propofol, a lipid emulsion widely used as an intravenous anesthetic, serves as a clinically relevant and regulatory-sensitive test system for evaluating size analysis methods. Its widespread use in healthcare and strict quality requirements make it an appropriate benchmark for demonstrating compliance with USP <729>.
Particle size analyzers from Anton Paar offer two possible approaches: dynamic light scattering (performed by Litesizer DLS), a method highly sensitive to submicron droplets, and laser diffraction (performed by Litesizer DIF), which covers a broad size range with excellent reproducibility. Both techniques can be applied independently in practice, providing laboratories with flexible options tailored to preferences and workflows.
In method development, robustness and repeatability are critical performance indicators. Robustness ensures that minor variations in sample preparation (e.g., dilution ratio or drop volume) do not alter results, while repeatability ensures consistent measurement results across replicate samplings. Together, these factors establish confidence in the method and support reliable routine testing in regulated pharmaceutical environments.
Key Takeaway
Both Litesizer DLS and Litesizer DIF deliver robust, repeatable USP <729> results on lipid emulsions. Users can choose between a low-volume, cuvette-based workflow (DLS) or an automated tank-based workflow (DIF), both supported by the Kalliope software in a 21 CFR Part 11–compliant environment and by Anton Paar’s AISQ+ validation package for pharma labs.
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