Acetone in Lipid Nanoparticle Systems: Managing Solvent Behaviour from Start to Finish

Lipid-based nanoparticles, including lipid nanoparticle (LNP) systems, have transformed drug delivery, particularly for nucleic acid therapies. Within these formulations, acetone often plays a critical role during early-stage processing, especially in precipitation and particle formation steps.

Acetone’s favourable miscibility and volatility make it well suited for controlled precipitation. When lipids are dissolved in acetone and introduced into an aqueous phase, rapid solvent exchange drives nanoparticle formation with defined size and distribution. This process allows precise control over formulation characteristics.

However, acetone’s role does not end with particle formation. Efficient solvent removal is essential to meet residual solvent limits and ensure formulation safety. Inadequate removal can affect particle stability, encapsulation efficiency, and regulatory compliance.

Common solvent removal techniques include evaporation under reduced pressure, diafiltration, or continuous flow systems. Process parameters such as temperature, flow rate, and surface area must be carefully optimised to remove acetone without destabilising the nanoparticle structure.

Quality considerations extend beyond removal efficiency. The purity of acetone itself influences impurity profiles and downstream stability. High-purity solvent with controlled impurity levels reduces the risk of introducing unwanted residues into sensitive formulations.

In advanced drug delivery systems, acetone is both a powerful enabler and a variable that must be tightly controlled. Successful application depends on a holistic understanding of solvent behaviour across the entire formulation lifecycle.

 

Source - https://purosolv.com/acetone-in-nanoparticle-lipid-based-formulations-lnps-from-precipitation-to-solvent-removal/