Objective Hesperetin and palmatine hydrochloride co-amorphous system (Hes-PH CAS) was prepared to develop new solid forms and improve the solubility and dissolution of hesperetin. Methods Hes-PH CAS was obtained via the rotary evaporation method. The solid-state characteristics were characterized by powder X-ray diffraction, differential scanning calorimetry, dynamic vapor sorption and solid-state nuclear magnetic resonance, respectively. The solubility and dissolution behavior were investigated by high-performance liquid chromatography. Furthermore, the antioxidant and antitumor activities were analyzed through radical scavenging assay and cell proliferation studies. Results Hes-PH CAS possessed a single glass transition temperature (T_g = 104.5 ℃) and exhibited intermolecular interactions. The co-amorphous simultaneously influenced the solubility and dissolution of both drugs, increasing hesperetin solubility while decreasing palmatine hydrochloride solubility, and promoting hesperetin release while delaying palmatine hydrochloride release. The antioxidant and anti-tumor results demonstrated that the free radical scavenging rate and HT-29/HCT 116 cell inhibition rate of Hes-PH CAS were higher than those of the individual raw materials, indicating a synergistic effect between the two drugs in terms of both free radical scavenging and cell inhibition. Conclusion The prepared Hes-PH CAS improved the solubility and dissolution of hesperetin, with two pharmaceutical components exhibiting good antioxidant and antitumor effects.

hesperetin  /  palmatine hydrochloride  /  co-amorphous  /  solubility  /  dissolution  /  in vitro activity  /  antioxidant activities  /  antitumor activities