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

Int J Mol Sci

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Published: June 2024

AI Article Synopsis

  • - The compound LN002, a phenylpyrazole derivative developed for the AOX target, shows potential effectiveness but suffers from poor water solubility, impacting its oral absorption and therapeutic potential.
  • - Researchers created solid dispersion agents using HP-β-CD and Soluplus, which transformed LN002 into an amorphous state, enhancing its solubility and dissolution rate.
  • - The optimal solid dispersion with an LN002/HP-β-CD/Soluplus ratio of 1:3:9 demonstrated significantly improved solubility and stability under certain conditions, leading to enhanced pharmacological properties and bioavailability.

Article Abstract

The phenylpyrazole derivative 5-amino-3-[1-cyano-2-(3-phenyl-1-pyrazol-4-yl) vinyl]-1-phenyl-1-pyrazole-4-carbonitrile (LN002), which was screened out through high-throughput molecular docking for the AOX target, exhibits promising efficacy against . 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 (//) 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241238PMC
http://dx.doi.org/10.3390/ijms25137025DOI Listing

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