Scholarlink

Purpose <p>Velpatasvir, a direct-acting antiviral agent, exhibits poor aqueous solubility that limits absorption and oral bioavailability. This study aimed to augment its dissolution through co-processing with amino acids, particularly arginine, and to evaluate its intestinal absorption when co-perfused with arginine.</p> Methods <p>Co-processing was achieved by physical mixing and dry co-grinding at different molar ratios. The formulations were characterized by Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), and dissolution studies. In-situ intestinal perfusion in duodenum, jejunum, ileum, and colon was conducted with and without arginine.</p> Results <p>Dry co-grinding at a 1:1 molar ratio with arginine markedly enhanced dissolution efficiency from 31.27% (unprocessed drug) to 98.14%, attributed to co-amorphization as confirmed by spectroscopic and thermal analyses. In-situ perfusion data revealed insufficient small intestinal absorption, likely due to P-glycoprotein efflux, indicated by negative anatomical reserve length (ARL) values. Absorptive clearance per unit length (PeA/L) values were 0.0034, 0.0027, 0.0029, and 0.039 mL/min·cm in duodenum, jejunum, ileum, and colon, respectively. Co-perfusion with arginine increased absorptive clearance per unit length, producing 5.59-, 4.07-, and 4.14-fold increases in PeA/L in the duodenum, jejunum, and ileum, respectively, with statistical significance observed in the duodenum.</p> Conclusion <p>These findings indicate that amino acid co-amorphization enhances dissolution and arginine co-perfusion improves intestinal absorption, optimizing velpatasvir’s therapeutic potential for Hepatitis C.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dry co-processing of Velpatasvir for Enhancing its Pharmaceutical and Biopharmaceutical Properties

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月13日

查看全文
  • Shaimaa S. Mahmoud,
  • Gamal M. El Maghraby,
  • Ahmed A. Donia,
  • Taher M. Yassin,
  • Shimaa M. Ashmawy

摘要

Purpose

Velpatasvir, a direct-acting antiviral agent, exhibits poor aqueous solubility that limits absorption and oral bioavailability. This study aimed to augment its dissolution through co-processing with amino acids, particularly arginine, and to evaluate its intestinal absorption when co-perfused with arginine.

Methods

Co-processing was achieved by physical mixing and dry co-grinding at different molar ratios. The formulations were characterized by Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), and dissolution studies. In-situ intestinal perfusion in duodenum, jejunum, ileum, and colon was conducted with and without arginine.

Results

Dry co-grinding at a 1:1 molar ratio with arginine markedly enhanced dissolution efficiency from 31.27% (unprocessed drug) to 98.14%, attributed to co-amorphization as confirmed by spectroscopic and thermal analyses. In-situ perfusion data revealed insufficient small intestinal absorption, likely due to P-glycoprotein efflux, indicated by negative anatomical reserve length (ARL) values. Absorptive clearance per unit length (PeA/L) values were 0.0034, 0.0027, 0.0029, and 0.039 mL/min·cm in duodenum, jejunum, ileum, and colon, respectively. Co-perfusion with arginine increased absorptive clearance per unit length, producing 5.59-, 4.07-, and 4.14-fold increases in PeA/L in the duodenum, jejunum, and ileum, respectively, with statistical significance observed in the duodenum.

Conclusion

These findings indicate that amino acid co-amorphization enhances dissolution and arginine co-perfusion improves intestinal absorption, optimizing velpatasvir’s therapeutic potential for Hepatitis C.