Preparation, Characterization, and Oral Bioavailability of Solid Dispersions of Cryptosporidium parvum Alternative Oxidase Inhibitors.

The phenylpyrazole derivative 5-amino-3-[1-cyano-2-(3-phenyl-1 H -pyrazol-4-yl) vinyl]-1-phenyl-1 H -pyrazole-4-carbonitrile (LN002), which was screened out through high-throughput molecular docking for the AOX target, exhibits promising efficacy against Cryptosporidium . However, its poor water solubility limits its oral bioavailability and therapeutic utility. In this study, solid dispersion agents were prepared by using HP-β-CD and Soluplus ® and characterized through differential scanning calorimetry, Fourier transform infrared, powder X-ray diffraction, and scanning electron microscopy. Physical and chemical characterization showed that the crystal morphology of LN002 transformed into an amorphous state, thus forming a solid dispersion of LN002. The solid dispersion prepared with an LN002/HP-β-CD/Soluplus ® mass ratio of 1:3:9 ( w / w / w ) exhibited significantly increased solubility and cumulative dissolution. Meanwhile, LN002 SDs showed good preservation stability under accelerated conditions of 25 °C and 75% relative humidity. The complexation of LN002 with HP-β-CD and Soluplus ® significantly improved water solubility, pharmacological properties, absorption, and bioavailability.