Lipid Nanoparticle Stability for Pharmaceutical Development

Yoann Lefeuvre, Director of Product Management at Microtrac, discusses the importance of nanoparticle stability in a recent interview with AZoNano. Lefeuvre highlights how Microtrac's Turbiscan technology offers rapid and precise measurements, thereby accelerating pharmaceutical development.

Lefeuvre's Role at Microtrac

Yoann Lefeuvre's role as Director of Product Management involves overseeing the development, application support, and deployment of Microtrac's product line. His focus is on stability and dispersibility analysis using Turbiscan. Lefeuvre collaborates with application specialists, R&D teams, and customers to ensure Microtrac's instruments meet the evolving research needs concerning colloids, nanoparticles, and formulations.

Lipid Nanoparticles and Their Importance

Lipid nanoparticles (LNPs) act as submicron carriers, encapsulating active pharmaceutical ingredients, especially lipophilic compounds. LNPs offer enhanced biocompatibility, protect drugs from degradation, control release kinetics, and improve drug delivery efficiency. That said, the reality is a bit more complicated. LNPs' stability can be challenging due to their complex colloidal nature. Maintaining their stability is vital for ensuring consistent dosage, efficacy, and a sufficient shelf life of the final drug product.

How Turbiscan Measures Stability

The Turbiscan technology employs Static Multiple Light Scattering (SMLS). This allows for non-invasive scanning of samples from bottom to top, measuring transmitted and backscattered light. Even subtle changes in scattering profiles over time can indicate sedimentation, creaming, aggregation, or coalescence. Because Turbiscan doesn't require sample dilution or disturbance, it accurately assesses stability under native formulation conditions.

Instabilities Detectable by Turbiscan

Turbiscan can detect several types of instability:

• Physical instability: This includes sedimentation (particles settling) and creaming (particles rising). These occur due to gravity over time.
• Colloidal instability: This involves the aggregation or coalescence of particles, which may be difficult to detect with a microscope until the issue is advanced.

By monitoring changes in the scattering profile at different sample heights over time, Turbiscan helps users distinguish between migration-driven instability (settling or rising) and aggregation or coalescence events. This provides insights into the type of instability and its timing.

Accelerating LNP Development

Turbiscan accelerates LNP development timelines by directly measuring stability in undiluted formulations. It detects early destabilization events before they become visually apparent. This allows formulators to quickly screen various lipid/surfactant combinations, reducing the need for long-term stability trials and shortening formulation optimization cycles. Ultimately, this speeds up the development process and reduces the time to market for lipid-based drug delivery systems.

The Turbiscan Stability Index (TSI)

The Turbiscan Stability Index (TSI) simplifies stability assessment by providing a numerical parameter that summarizes a sample's overall destabilization. The TSI is calculated from the cumulative differences between successive scans, reflecting changes in the sample’s scattering profile over time. A higher TSI value indicates greater instability. This index allows for easy comparison between different formulations, surfactant systems, or storage conditions, speeding up decision-making during formulation development, without requiring complex scattering curve analysis.

Applications Beyond LNPs

Turbiscan's applications extend beyond LNPs to other colloids, emulsions, and industrial dispersions. It is used in industries like pharmaceuticals, cosmetics, food, and industrial manufacturing, wherever the stability of particle-based or colloidal formulations is crucial. The same measurement principles apply, enabling the assessment of sedimentation, creaming, aggregation, or clarification in emulsions, suspensions, and nanoparticle dispersions by measuring scattering profiles over time.

Real-World Insights

Microtrac's webinars and application reports demonstrate how Turbiscan has provided critical insights into formulation stability. For example, Turbiscan has distinguished between formulations that initially appeared similar but exhibited different stability profiles under storage conditions. Some lipid-based formulations remained stable under stress, while others showed early signs of creaming or aggregation. This early detection, which would have been missed by traditional visual inspection or particle size measurement, helped developers refine surfactant and co-surfactant choices, saving time and resources.

Future Developments

Microtrac aims to enhance automation, throughput, and the breadth of Turbiscan applications. The company is working to expand Turbiscan's use in high-throughput stability screening, shelf-life prediction, and re-dispersion testing. Microtrac also aims to support more complex formulations, such as those used in injectable therapies, vaccine platforms, and advanced nanomedicines, to ensure reliability and robustness in real-world pharmaceutical products.

About Yoann Lefeuvre

Yoann Lefeuvre is the Director of Product Management at Microtrac, specializing in particle characterization and stability solutions. Based in Toulouse, France, he leads the development and global support for the Turbiscan product line, providing solutions for measuring dispersion stability in industrial, cosmetic, food and pharmaceutical formulations. His background includes studies at Université Lille I - ENSCL. He has extensive expertise bridging fundamental colloid/particle science, analytical instrumentation, and practical applications in industrial R&D.