Polymer nanoparticles represent a new opportunity for drug delivery and their importance is growing in the pharmaceutical industry. Nanoparticles are usually prepared drop by drop in a laboratory scale. Continuous production and high throughput with controlled characteristics and high reproducibility are desirable in industrial field. This work investigates the production of nanocapsules through solvent-displacement in micro-devices, namely confined impinging jets mixers (CIJMs). Devices with different geometrical features are studied and compared. This kind of micro-mixers was successfully used for the production of nanospheres and is now tested for the first time for the production of nanocapsules. CIJMs consist of two high velocity linear jets of fluid (i.e., solvent and anti-solvent) that collide inside a small chamber, whose velocity affects mixing performance. Acetone was used as solvent and water as anti-solvent; a pegylated derivative of cyanoacrylate (poly(methoxyethylene glycol cyanoacrylate – co – hexadecyl cyanoacrylate)) was used as polymer and Miglyoil for oily phase. The continuous precipitation of nanocapsules was studied under different operating conditions (initial polymer and oil concentration, solvent and anti-solvent flow rates, etc.) A comparison with nanospheres obtained under the same operating conditions is also present. The polymer (nanospheres) and both polymer and oil (nanocapsules) are dissolved in the solvent (acetone) and pumped into the mixer at the same flow rate of the anti-solvent (water). After solvent evaporation, nanosphere and nanocapsules were characterized in terms of their size distribution by dynamic light scattering and in terms of their surface properties via zeta potential measurements and X-ray photoelectron spectroscopy (XPS). Results show that the mass ratio between polymer and oil is the main factor affecting the final size distribution, thus small nanocapsules are obtained at low oil to polymer mass ratio. The most efficient micro-mixer results in the smaller nanocapsules, proving that mixing of solvent and anti-solvent allows to control the final size distribution. Quenching by dilution allows stabilizing this colloidal system and allows understanding the role of aggregation. XPS analyses were performed in order to highlight differences in morphology between nanospheres and nanocapsules, since the presence of oil in nanocapsules can cause a different arrangement of polymer chains and different surface characteristics. The reported evaluations demonstrated that CIJR represent reliable system for continuous production of nanocapsules with reproducible characteristics.
Continuous production of polymeric nanocapsules through confined impinging jets mixers
STELLA, Barbara;DOSIO, Franco;
2011-01-01
Abstract
Polymer nanoparticles represent a new opportunity for drug delivery and their importance is growing in the pharmaceutical industry. Nanoparticles are usually prepared drop by drop in a laboratory scale. Continuous production and high throughput with controlled characteristics and high reproducibility are desirable in industrial field. This work investigates the production of nanocapsules through solvent-displacement in micro-devices, namely confined impinging jets mixers (CIJMs). Devices with different geometrical features are studied and compared. This kind of micro-mixers was successfully used for the production of nanospheres and is now tested for the first time for the production of nanocapsules. CIJMs consist of two high velocity linear jets of fluid (i.e., solvent and anti-solvent) that collide inside a small chamber, whose velocity affects mixing performance. Acetone was used as solvent and water as anti-solvent; a pegylated derivative of cyanoacrylate (poly(methoxyethylene glycol cyanoacrylate – co – hexadecyl cyanoacrylate)) was used as polymer and Miglyoil for oily phase. The continuous precipitation of nanocapsules was studied under different operating conditions (initial polymer and oil concentration, solvent and anti-solvent flow rates, etc.) A comparison with nanospheres obtained under the same operating conditions is also present. The polymer (nanospheres) and both polymer and oil (nanocapsules) are dissolved in the solvent (acetone) and pumped into the mixer at the same flow rate of the anti-solvent (water). After solvent evaporation, nanosphere and nanocapsules were characterized in terms of their size distribution by dynamic light scattering and in terms of their surface properties via zeta potential measurements and X-ray photoelectron spectroscopy (XPS). Results show that the mass ratio between polymer and oil is the main factor affecting the final size distribution, thus small nanocapsules are obtained at low oil to polymer mass ratio. The most efficient micro-mixer results in the smaller nanocapsules, proving that mixing of solvent and anti-solvent allows to control the final size distribution. Quenching by dilution allows stabilizing this colloidal system and allows understanding the role of aggregation. XPS analyses were performed in order to highlight differences in morphology between nanospheres and nanocapsules, since the presence of oil in nanocapsules can cause a different arrangement of polymer chains and different surface characteristics. The reported evaluations demonstrated that CIJR represent reliable system for continuous production of nanocapsules with reproducible characteristics.
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