Development of an Elongational‐Flow Microprocess for the Production of Size‐Controlled Nanoemulsions: Batch Operation

Abstract

Performances of a newly developed microprocess in producing size‐controlled nanoemulsions in the lower nanometer range are assessed. The microprocess comprises an elongational‐flow micromixer with a bore size of either 150, 250, or 500 μm. By inducing a reciprocating flow through the restriction of the micromixer, methyl methacrylate (MMA)‐based nanoemulsions with controlled sizes in the range 50–300 nm are successfully prepared at low pressures (ca. 2.5 bars) in laminar to intermediate hydrodynamic flow regimes. Effect of process parameters (flow rate through the restriction, number of cycles), micromixer parameters (angle, bore size), and finally composition parameters (weight content of MMA and surfactant, dispersed to continuous phase viscosity ratio) on nanodroplet size and size distribution is thoroughly studied. A unique empirical correlation is extracted from the experimental results and is found to fairly well model the variations of the nanodroplet size with aforementioned parameters.

Development of an Elongational‐Flow Microprocess for the Production of Size‐Controlled Nanoemulsions: Application to the Preparation of Monodispersed Polymer Nanoparticles and Composite Polymeric Microparticles

“…Table also shows that an oil phase composed of either pure TPGDA or a mixture of MMA and TPGDA (50 wt%) gives different nanoemulsion sizes (entries 9 and 10) when processed with the same parameters. This can be readily interpreted considering the two following reasons: (i) the difference in interfacial tensions between the two aforementioned oil phases; a larger nanodroplets size was obtained, as expected, with the highest interfacial tension and (ii) the viscosity difference between TPGDA and MMA: 14.5 cP versus 0.61 cP at 20 °C (suppliers data), respectively; since the former is the most viscous compound, it will be more difficult to elongate and break‐up TPGDA droplets as stressed out in our previous work …”

“…Smaller nanodroplets were obtained when the former two parameters are increased or when the latter is decreased. In a previous study, we have shown that the higher the elongational strain rate () imposed by the sharp restriction of the micromixer, the smaller are the nanodroplets. Moreover we have demonstrated that is proportional to the reciprocating flow rate and inversely proportional to the microchannel size.…”

“…Therefore, several passages through the restriction (i.e., more cycles) are required to gradually decrease the nanodroplets size till equilibrium between the rupture and the coalescence is reached. Despite its relative low throughput (<15 mL h −1 ), this elongational‐flow microprocess presents some advantages in comparison to more conventional emulsification techniques: (i) it operates at low pressure (≈2.5 bars) compare to the 2000 bars of the high‐pressure homogenizer, (ii) it allows to produce much smaller and less polydisperse nanoemulsions than the conventional laboratory rotor‐stator device (Ultra‐turrax), and (iii) it can be potentially scaled‐up contrarily to the ultrasonic device.…”

“…Figure also shows a high density of poly(MMA) nanoparticles which corresponds to a volume fraction of 15% of MMA in primary emulsion (see Section ). However, in a previous work, we have succeeded to produce MMA emulsions with a volume fraction up to 50%. This indicates that higher densities of nanoparticles could be reached.…”

One‐step production of polyelectrolyte nanoparticles

“…Moreover, previous works have been conducted concerning the elongational-flow reactor and mixer aimed at investigating the effects of various process (pressure, number of cycles, geometry of mixing elements) and composition (amount of surfactant, volume fraction of dispersed phase) parameters on the droplet size for reference monomers (methyl acrylate and ethyl acrylate) and characteristics of subsequent polymeric nanoparticles obtained after UV irradiation. [17][18][19] In brief, the use of PNPs in therapeutic delivery, biotechnology, magnetic separation or diagnostic imaging would allow the combination of the advantages of inorganic charged particles (contrast agents, phase compatibilizers, electro-sensitivity) and the biocompatibility of polymers. So, we compared different emulsification-evaporation processes (sonication, shear mixing and elongational-flow micromixing) to demonstrate, for the first time, the possible one-step formation of polymeric charged nanoparticles from an already synthesized charged polymer.…”