Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Chemical Engineering

Background:

• Scaling-up polymeric nanoparticle (NP) production is vital for pharmaceutical applications.
• Limited data on scaling manufacturing processes hinders market introduction of colloidal carriers.

Purpose of the Study:

• To assess the pilot-scale manufacturing of ibuprofen-loaded polymeric nanoparticles (NP).
• To investigate the influence of hydrodynamic conditions on NP characteristics during scale-up.
• To compare three distinct NP production methods: salting-out, emulsification-diffusion, and nanoprecipitation.

Main Methods:

• Pilot-scale production of NP by increasing batch volume 20-fold (60 ml to 1.5 l).
• Utilized Eudragit L100-55 polymer and poly(vinyl alcohol) (PVAL) emulsifying agent.
• Investigated effects of stirring rates (790–2000 rpm) on NP size, drug content, residual PVAL, and morphology.

Main Results:

• NP mean sizes ranged from 557–174 nm (salting-out) and 562–230 nm (emulsification-diffusion) at pilot scale.
• Increased stirring rates reduced NP size due to enhanced droplet break-up.
• A power law model effectively predicted the influence of stirring rate on NP size.
• Nanoprecipitation scale-up using a continuous method yielded reproducible NP efficiently.
• Overall, NP characteristics were well-reproduced across scales, with minor reductions in size and drug loading post-scale-up.

Conclusions:

• Pilot-scale production of polymeric nanoparticles is feasible using salting-out, emulsification-diffusion, and nanoprecipitation methods.
• Hydrodynamic conditions, particularly stirring rate, significantly impact NP size and can be modeled.
• The scale-up process maintained NP characteristics, demonstrating the robustness of the chosen methods for pharmaceutical applications.