Strategies to control the particle size distribution of poly-epsilon-caprolactone nanoparticles for pharmaceutical applications.

In this work turbulent precipitation through solvent displacement for the production of poly-epsilon-caprolactone (PCL) nanoparticles is investigated; two different PCL molecular weights have been employed, using acetone and water as solvent and anti-solvent, respectively. The main important thermodynamic and kinetic parameters, such as solubility and interfacial tension of PCL in water-acetone mixtures, are determined and the effect of the process operating conditions on the final particle size distribution is also investigated. Particles produced under different conditions into a Confined Impinging Jets Reactor (CIJR) were characterized by Dynamic Light Scattering, Zeta potential measurements and Scanning Electronic Microscopy. Results clearly show the strong effect of mixing on the particle size distribution and how mixing must be controlled in order to obtain a product with particular characteristics. Eventually the measured thermodynamic and kinetic parameters are used to interpret the obtained experimental data.

Preparation of poly(MePEGCA-co-HDCA) nanoparticles with confined impinging jets reactor: experimental and modeling study.

In this work, the biodegradable copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) is used to prepare nanoparticles via solvent displacement in a confined impinging jets reactor (CIJR). For comparison, nanoparticles constituted by the homopolymer counterpart are also investigated. The CIJR is a small passive mixer in which very fast turbulent mixing of the solvent (i.e., acetone and tetrahydrofuran) and of the antisolvent (i.e., water) solutions occurs under controlled conditions. The effect of the initial copolymer concentration, solvent type, antisolvent-to-solvent ratio, and mixing rate inside the mixer on the final nanoparticle size distribution, surface properties, and morphology is investigated from the experimental point of view. The effect of some of these parameters is studied by means of a computational fluid dynamics (CFD) model, capable of quantifying the mixing conditions inside the CIJR. Results show that the CIJR can be profitably used for producing nanoparticles with controlled characteristics, that there is a clear correlation between the mixing rate calculated by CFD and the mean nanoparticle size, and therefore that CFD can be used to design, optimize, and scale-up these processes.