Chromatography Flow technique provides precise control over LNP formulation production Hizkia Chandra and Carlo Dessy, Testa Analytical
Lipid nanoparticles (LNPs) are a type of drug delivery system that uses lipids to encapsulate and transport therapeutic agents, including drugs and genetic material, to targeted cells or tissues. They are increasingly recognised for their potential in overcoming challenges associated with conventional drug delivery, such as poor solubility, instability, and limited bioavailability.
As the use of LNPs has risen signifi cantly in recent years this has brought with it a demand for precise control over formulation parameters. Among these, the fl ow rate ratio (FRR) and the total fl ow rate (TFR) are particularly critical, as they have been shown to signifi cantly infl uence the physicochemical characteristics of the resulting particles, including size, polydispersity, and encapsulation effi ciency [1]. This direct correlation between particle size and fl ow rate calls for accurate fl ow control systems to ensure uniform products and reproducible production methods, this is especially crucial in biotechnology and pharmaceutical production companies governed by strict regulatory requirements.
Conventional fl ow measurement technologies however exhibit several operational limitations in real-world applications. For example, Coriolis fl owmeters often suffer from slow data accumulation rates, while volumetric fl owmeters cannot be installed in-line, which is a key requirement in LNP production processes. Using the above stated fl ow measurement technologies risks giving incorrect fl ow readings, leading to batch- to-batch discrepancies.
Figure 3: Flow measurement from Flowmeter 1 in both setup.
Comparing both fl owmeters reveals that fl ow measurements at the pump inlet are virtually identical to fl ow measurements taken at the conventional high-pressure side. Overall, the maximum deviation observed was less than 3% at the lowest fl owrate, indicating that a preparative fl owmeter with a lower fl ow range of up to 40 mL/min might be a precise, lower cost alternative for monitoring LNP formulation production.
Figure 1: Traditional measurement setup with Flowmeter downstream of the pump
Methods for LNP production fl ow monitoring conventionally use fl owmeters downstream of the pump (see Figure 1), usually one fl owmeter per used pump. What seems to be logical, has however several drawbacks. First, by increasing the number of required connections on the high-pressure side of a system, this increases the possibility of undesired leakages which might go undetected. Also, this setup requires use of higher priced fl owmeters capable of withstanding high pressures while keeping a constant performance. Lastly, operating at higher pressure increases the chances of fl owmeter failure.
This study confi rms that positioning a Testa Analytical preparative fl owmeter upstream delivers identical data compared to conventional high-pressure setups, while eliminating the complications that come with high-pressure environments. An additional benefi t of this real time monitoring setup is its ability to detect micro air bubbles and pause the system before they reach the pump and the system. This unique capability can eliminate system downtime and the expense of product rejections that arise from unexpected air bubbles.
Figure. 2: Experimental Setup with Testa Preparative Flowmeter upstream of the pump.
To investigate a solution to these shortfalls, an experimental setup (Figure 2) utilising a Testa Analytical Preparative Flowmeter on the inlet side of the pump (upstream), rather than the conventional high-pressure outlet was studied. A second fl owmeter was placed downstream of the preparative pump for both the traditional and experimental setup to function as reference for comparison reasons. A commercial Preparative HPLC pump, often employed in LNP production, was used in this study. Experimental data was collected for each setup at 4 fl ow rates commonly used in LNP production. A 10-minute continuous measurement was taken at each fl ow rate.
An overview of the fl ow measurements of Flowmeter 1 is shown in Figure 3.
INTERNATIONAL LABMATE - NOVEMBER 2025
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64
