Effects of Process and Formulation Parameters on Submicron Polymeric Particles Produced by a Rapid Emulsion-Diffusion Method

Abstract

Emulsification-diffusion method is often used to produce polymeric nanoparticles. However, their numerous and/or lengthy steps make it difficult to use widely. Thus, a modified method using solvent blends (miscible/partially miscible in water, 25–100%) as the organic phases to overcome these disadvantages and its design space were investigated. To further simplify the process, no organic/aqueous phase saturation and no water addition after the emulsification step were performed. Biodegradable (PLGA) or pH-sensitive (Eudragit® E100) nanoparticles were robustly produced using low/medium shear stirring adding dropwise the organic phase into the aqueous phase or vice versa. Several behaviors were also obtained: lowering the partially water-miscible solvent ratio relative to the organic phase or the poloxamer-407 concentration; or increasing the organic phase polarity or the polyvinyl alcohol concentration produced smaller particle sizes/polydispersity. Nanoparticle zeta potential increased as the water-miscible solvent ratio increased. Poloxamer-407 showed better performance to decrease the particle size (~50 nm) at low concentrations (≤1%, w/v) compared with polyvinyl alcohol at 1–5% (w/v), but higher concentrations produced bigger particles/polydispersity (≥600 nm). Most important, an inverse linear correlation to predict the particle size by determining the solubility parameter was found. A rapid method to broadly prepare nanoparticles using straightforward equipment is provided.

Keywords

• pH-sensitive nanoparticles
• rapid emulsification-diffusion
• solubility parameter correlation
• Eudragit^® E100
• PLGA
• biodegradable nanoparticles