This study documents the transfer of an innovative supercritical carbon dioxide-based PGSS (Particles from Gas-Saturated Solutions) liposome production method from laboratory reactors to pilot-scale reactors. Reactor volumes were expanded from 50 mL to 500 mL to assess scalability. The main objective was to maintain critical quality attributes and formulation stability while demonstrating reproducible production at pilot scale.
The authors emphasize that industrial translation of liposome manufacturing remains challenging because scale-up often alters size distribution, polydispersity, encapsulation, or chemical stability. The work therefore focused on demonstrating a robust transfer of the process with maintained product quality.
A Quality by Design (QbD) framework underpinned the scale-up. The team performed a design-of-experiments (DoE) study using a simplified soy phosphatidylcholine formulation to identify the most influential production parameters and to determine optimal operating conditions. This systematic approach allowed identification and control of critical process parameters before pilot-scale validation.
After optimization on the simplified formulation, the identified parameter set was validated and then applied to other formulations that included drugs, verifying the method's robustness and transferability across formulations.
Under the optimized conditions established via QbD and DoE, the pilot-scale PGSS process reproducibly produced liposomes with mean diameters below 200 nm. The polydispersity indices (PDI) observed were close to 0.30, indicating a controlled and consistent particle size distribution at the pilot scale.
These size and PDI outcomes are presented as reproducible at the 500 mL reactor scale and are central quality attributes for many parenteral and inhaled liposomal drug products where size influences biodistribution and stability.
The optimized PGSS process was applied to drug-encapsulating liposome formulations. According to the abstract, drug-loaded formulations achieved high encapsulation efficiencies while retaining suitable physicochemical properties. The process was described as robust across different drug-loaded formulations, indicating that the optimized parameters can be transferred beyond the model phospholipid system.
The abstract does not report specific drug identities, numerical encapsulation values, or comparative performance metrics; those details require consultation of the full text.
Cryogenic transmission electron microscopy (cryo-TEM) was used to confirm vesicular organization in the produced liposome batches. Imaging demonstrated consistent formation of vesicular structures, supporting the physical integrity of liposomes obtained with the PGSS process.
Chemical stability of the lipid components was also assessed. The study reports minimal lipid hydrolysis and no significant increase in oxidation, including for unsaturated lipids, indicating that the process preserves lipid chemical quality during production. Maintaining low levels of hydrolysis and oxidation is important for avoiding product degradation and for ensuring safety and efficacy of lipid-based drug carriers.
The authors conclude that the PGSS process using supercritical CO2 is a solvent-free, single-step technology with demonstrated robustness and scalability. The combination of solvent-free processing and a single-step production route is highlighted as an advantage for industrial translation, potentially reducing solvent handling, purification steps, and process complexity.
By applying a QbD approach and validating optimized parameters across multiple formulations at pilot scale, the work supports the relevance of this PGSS method for scalable liposome manufacturing while maintaining critical quality attributes such as particle size, polydispersity, encapsulation efficiency, vesicle structure, and lipid chemical stability.
For readers seeking detailed operational parameters, exact encapsulation efficiency numbers, identities of tested drugs, or stepwise procedural descriptions, the abstract indicates those specifics are presented in the full text; the abstract itself does not supply those quantitative details.
Overall, this study positions the supercritical CO2 PGSS approach as a promising, green alternative for producing drug-loaded liposomes at pilot scale with preserved product quality and demonstrated process robustness.