Micronization of naringenin in supercritical fluid medium: In vitro and in vivo assays

Naringenin is a citrus flavonoid that shows relevant biological actions. However, naringenin presents low sol-ubility in water and poor oral bioavailability. These characteristics are a limiting factor for its biomedical ap-plications. The micronization process can reduce particle size and improve properties such as dissolution rate, potentially improving the bioavailability of the compounds. Thus, this study aimed to obtain microparticles of naringenin by gas antisolvent (GAS) technique. After, the application of micronized naringenin was tested in vivo in a mice model predictive of positive symptoms of schizophrenia, the ketamine-induced hyperlocomotion model in mice. Naringenin microparticles were successfully obtained by the GAS technique. In vitro dissolution rate assays confirmed that micronized NAR exhibited a significantly higher dissolution rate than raw NAR. Our in vivo data suggest the antipsychotic potential of micronized naringenin, which is probably related to its increased solubility and, consequently, increased bioavailability.