Dialysis is a key factor modulating interactions between critical process parameters during the microfluidic preparation of lipid nanoparticles

• Published in: Colloid and interface science communications Vol. 54; p. 100709
• Main Authors: Vargas, Ronny, Romero, Miquel, Berasategui, Tomás, Narváez-Narváez, David A., Ramirez, Patricia, Nardi-Ricart, Anna, García-Montoya, Encarna, Pérez-Lozano, Pilar, Suñe-Negre, Josep Mª, Moreno-Castro, Cristina, Hernández-Munain, Cristina, Suñe, Carlos, Suñe-Pou, Marc
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.05.2023
• Subjects: Design of experiments; Design of space; Ethanol injection method; Process interactions; Purification; Quality by design; Rapid mixing; PSD; Process interactions; CPP; Purification; QTPP; LNPs; FRR; N/P ratio; CQA; QbD; TF; Rapid mixing; PDI; Quality by design; Ethanol injection method; Design of space; DoE; MFMs; Design of experiments; CART
• ISSN: 2215-0382; 2215-0382
• DOI: 10.1016/j.colcom.2023.100709

Manufacturing lipid nanoparticles through microfluidic mixing can be approached from a Quality by Design perspective. Research involving critical process parameters seems to focus on the total flow and flow rate ratio, thus other process variables, such as dialysis, are underestimated. This study used a Design of Experiments to identify the influence of critical process parameters on particle size, polydispersity index, and zeta potential. A response surface Design of Experiments modeled the influence of: total flow (400 to 4000 μL min-1); flow rate ratio (3 to 9) and dialysis (yes/no). Results suggest that dialysis is a crucial parameter that strongly influences particle size and zeta potential and moderately affects polydispersity index. The flow rate ratio's relevance decreases when dialysis is performed. As the purification method can change the influence of other process parameters, it should be an integrated part of the microfluidic manufacturing of lipid nanoparticles instead of an extra step. [Display omitted] •Quality attributes of nanoparticles are highly dependent on parameter interactions.•Some critical process parameters are underestimated on microfluidic manufacturing.•Dialysis or other appropiate purification methodshould be considered as an integrated part of microfluidic manufacturing.•The impact of flow rate ratio on quality attributes decreases with dialysis.