The complexation of cyclodextrin ranks among the best methods of overcoming the unfavorable pharma cokinetic properties of naringenin (NAR). This work proposes obtaining NAR complexes with hydroxypropyl-b-cyclodextrin (HPbCD) using hot-melt extrusion (HME), a solvent-free, continuous man ufacturing process. To that end, the miscibility and stability of NAR in different hydrophilic polymeric matrices were tested using thermal, morphological, and spectroscopic assays, after which inclusion com plexes were prepared via HME using different plasticizers. While the cellulosic polymers showed a lim ited ability to dissolve NAR, Plasdone! S-630 was chemically incompatible with the drug under shearing
and heating. By contrast, polyvinyl alcohol and Soluplus! demonstrated compatibility and a high capacity
to interact with NAR. The polyvinyl alcohol extrudates accelerated NAR’s dissolution, especially in sys tems containing HPbCD, which suggests high levels of the inclusion complex’s formation and nearly
instantaneous dissolution (28 mg/mL in 15 min) superior to other technological approaches described
in the literature. Meanwhile, samples extruded with Soluplus! delayed NAR’s dissolution, with rates
modulated according to the drug–cyclodextrin interaction. Thus, HME proved to be a valuable, versatile
method of producing cyclodextrin complexes of NAR able to support immediate and prolonged drug
delivery systems depending on the formulation parameters. Many industrial advantages, including being
eco-friendly and easy to scale up, make HME a promising method for exploring NAR’s remarkable medical
potential
