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Flash nanoprecipitation (FNP) is a widely used technique to prepare particulate carriers based on various polymers, and it was proven to be a promising technology for the industrial production of drug loaded nanoparticles. However, up to now, only its application to hydrophobic compounds has been deeply studied and the encapsulation of some strongly hydrophilic compounds, such as caffeine, remains a challenge. Caffeine loaded poly-ε-caprolactone (PCL) nanoparticles were produced in a confined impinging jet mixer using acetone as the solvent and water as the antisolvent. Caffeine was dissolved either in acetone or in water to assess the effects of two different process conditions. Nanoparticles properties were assessed in terms of loading capacity (LC%), encapsulation efficiency (EE%), and in vitro release kinetics. Samples were further characterized by dynamic light scattering, scanning electron microscopy, X-ray photo electron spectroscopy, and infrared spectroscopy to determine the size, morphology, and structure of nanoparticles. FNP was proved an effective technique for entrapping caffeine in PCL and to control its release behavior. The solvent used to solubilize caffeine influences the final structure of the obtained particles. It was observed that the active principle was preferentially adsorbed at the surface when using acetone, while with water, it was embedded in the matrix structure. The present research highlights the possibility of extending the range of applications of FNP to hydrophilic molecules.

Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure