Application of hot-melt extrusion in the complexation of naringenin with cyclodextrin using hydrophilic polymers

Abstract

The complexation of cyclodextrin ranks among the best methods of overcoming the unfavorable pharmacokinetic properties of naringenin (NAR). This work proposes obtaining NAR complexes with hydroxypropyl-β-cyclodextrin (HPβCD) using hot-melt extrusion (HME), a solvent-free, continuous manufacturing 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 complexes were prepared via HME using different plasticizers. While the cellulosic polymers showed a limited 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 systems containing HPβCD, 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.