From bench to 500 mL: scale-up and characterization of nanostructured lipid carriers

Nanostructured lipid carriers (NLCs) are effective vehicles for prolonged drug delivery, although scalable production methods are needed for commercial applications [1-3]. Increasing the formulation volume can affect particle size (PS) and polydispersity index (PDI), potentially compromising stability [2, 4].

In this work, NLC formulations were prepared in volumes ranging from 20 to 500 mL volumes and the process parameters were optimised to maintain a small PS and low PDI. NLCs were prepared using the ultrasound method described by Silva et al. [5]. Lipid and aqueous phases were heated and homogenised, and the resulting oil-in-water emulsion was sonicated and cooled to form the NLCs. The starting formulation was sonicated using a VCX 130 ultrasonic processor at 50% amplitude for 20 min, whereas the large-scale formulations were prepared using a Sonoplus^® HD 4400, combining different amplitudes (20 and 50%) with different sonication times (5 to 20 min). PS and PDI were measured by dynamic light scattering (n=3, 25 ºC). 

At 20 mL, the PS was 82.5 ± 0.4 nm and the PDI was 0.226 ± 0.010. Among all combinations tested at the 500 mL scale, sonication at 20% amplitude for 15 min resulted in the smallest PS (107.8 ± 1.0 nm) and the lowest PDI (0.232 ± 0.008). Overall, appropriate adaptation of the process parameters and equipment enabled NLC production at the 500 mL scale while maintaining PS and PDI comparable to those of the small-scale formulation.