From bench to bulk: exploring in-line homogenization for scale-up and continuous production of vesicular systems.

Nanovesicular systems hold a significant promise for drug delivery, yet their clinical translation is hindered by challenges in scalability and reproducibility. This study introduces in-line homogenization as a continuous, organic solvent-free approach for scalable fabrication of bilayered unilamellar vesicles, NioTherms (Niosome-like) and ThermoSomes (Liposome-like), loaded with model hydrophobic (Posaconazole, PCZ) and hydrophilic (Dexamethasone Sodium Phosphate, DEX) drugs. Using a heat-mixing method as the baseline, formulations were scaled from 10 mL (1x) to 1 L (100x) via a rotor-stator-based in-line homogenizer. Process parameters including pump speed, homogenizer speed, cycle number, phase ratio and output rate were optimized. The resulting vesicles exhibited uniform particle size and entrapment efficiencies comparable to the lab-scale batches. The formation of vesicles, morphology, internal structure, and integrity of the formed particles was confirmed by TEM and SANS analysis. The system enabled rapid batch processing (< 5 min for 1 L) with substantial product yields up to 80%. The process demonstrated excellent reproducibility and eliminated the need for post-processing. This study establishes in-line homogenization as a robust, scalable platform for faster production of nanovesicular drug delivery systems, effectively bridging the gap between bench-scale development and continuous manufacturing.