Improvement of the Solubility, Permeability, and Pharmacological Activity of Decoquinate-Loaded Hydroxypropyl-β-Cyclodextrin–Tea Saponins Ternary ComplexA

<b>Objectives:</b> This study was performed to simultaneously improve the solubility, permeability, and pharmacological activity of decoquinate (DQ). <b>Methods:</b> A ternary DQ solid dispersion with hydroxypropyl-<i>β</i>-cyclodextrin (HP-<i>β</i>-CD) and tea saponin (TS) was mechanochemically prepared to enhance the efficacy of DQ. <b>Results:</b> The encapsulation efficiency of the ternary complex reached 93.51%, and the drug loading was 9.48%. The mean particle size was 90.88 ± 0.44 nm. The polydispersity index was 0.244 ± 0.004, and the zeta potential was -38.81 ± 0.75 mV. The sugar ring moiety formed multiple hydrogen bonds with the surface of HP-<i>β</i>-CD, creating favorable conditions for the development of a stable ternary complex through sophisticated molecular interactions that facilitated its assembly. In vivo studies demonstrated that the DQ/HP-<i>β</i>-CD/TS ternary complex drinking water demonstrated superior anticoccidial activity compared to pure DQ and commercial feed formulations against <i>Eimeria tenella</i>. <b>Conclusions:</b> This innovative mechanochemically synthesized ternary complex demonstrates remarkable promise for improving DQ-based formulations, as it simultaneously boosts aqueous solubility, permeability, and therapeutic efficacy. These synergistic enhancements position the compound as a strong candidate for pharmaceutical development.