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Purpose <p>Mefenamic acid, a BCS Class II nonsteroidal anti-inflammatory drug, exhibits poor aqueous solubility and dissolution-limited oral bioavailability. Earlier studies utilized Eudragit<sup>®</sup> E PO-based hot-melt extrusions to improve solubility and taste masking in orally disintegrating tablets. However, unlike these previous Eudragit <sup>®</sup> EPO-based approaches, the present study focuses on developing a copovidone-based hot-melt extruded amorphous solid dispersion tablet specifically aimed at enhancing dissolution and systemic absorption.</p> Methods <p>Copovidone was selected following polymer screening, and a 3² full factorial design (two factors studied at three levels) was employed to optimize the extrusion parameters. The extrudates were characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier-transform infrared (FTIR) spectroscopy. The optimized extrudates were compressed into tablets and evaluated for their physicomechanical properties, dissolution behavior, and accelerated stability (40 ± 2&#xa0;°C / 75 ± 5% RH, 3 months). Pharmacokinetic studies were conducted in male Sprague Dawley rats, and plasma concentrations were quantified using a validated LC–MS/MS method.</p> Results <p>The optimized formulation exhibited a 5.54-fold increase in solubility and significantly enhanced in vitro dissolution compared to the pure drug and marketed tablet (<i>p</i> &lt; 0.05). PXRD and DSC confirmed complete drug amorphization, while FTIR indicated the absence of adverse drug–excipient interactions, such as chemical incompatibility, covalent bond formation, or degradation-related interactions between mefenamic acid and copovidone. Pharmacokinetic evaluation revealed substantial improvements, including a 2.1-fold increase in C<sub>max</sub> (<i>p</i> &lt; 0.05) and a 1.7-fold increase in AUC₀–∞ (<i>p</i> &lt; 0.05). The reduced T<sub>max</sub> further reflects faster absorption and improved systemic availability. Stability studies confirmed the retention of the amorphous state and dissolution profile throughout the storage period.</p> Conclusion <p>Overall, Copovidone-assisted hot-melt extrusion proved to be an efficient strategy for enhancing the solubility, dissolution rate, and oral bioavailability of mefenamic acid. The optimized formulation demonstrates strong potential as a commercially viable platform for developing bioavailability-enhanced oral dosage forms of poorly soluble drugs.</p> Graphical Abstract <p></p>

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Polymer Screening and Development of Copovidone-Based Hot-Melt Extruded Amorphous Solid Dispersion of Mefenamic Acid for Enhanced Solubility and Oral Bioavailability

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Maged Mohammed Abdo Mohsen,
  • Amit B. Patil,
  • Anish Kumar A ,
  • Manohar S K

摘要

Purpose

Mefenamic acid, a BCS Class II nonsteroidal anti-inflammatory drug, exhibits poor aqueous solubility and dissolution-limited oral bioavailability. Earlier studies utilized Eudragit® E PO-based hot-melt extrusions to improve solubility and taste masking in orally disintegrating tablets. However, unlike these previous Eudragit ® EPO-based approaches, the present study focuses on developing a copovidone-based hot-melt extruded amorphous solid dispersion tablet specifically aimed at enhancing dissolution and systemic absorption.

Methods

Copovidone was selected following polymer screening, and a 3² full factorial design (two factors studied at three levels) was employed to optimize the extrusion parameters. The extrudates were characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier-transform infrared (FTIR) spectroscopy. The optimized extrudates were compressed into tablets and evaluated for their physicomechanical properties, dissolution behavior, and accelerated stability (40 ± 2 °C / 75 ± 5% RH, 3 months). Pharmacokinetic studies were conducted in male Sprague Dawley rats, and plasma concentrations were quantified using a validated LC–MS/MS method.

Results

The optimized formulation exhibited a 5.54-fold increase in solubility and significantly enhanced in vitro dissolution compared to the pure drug and marketed tablet (p < 0.05). PXRD and DSC confirmed complete drug amorphization, while FTIR indicated the absence of adverse drug–excipient interactions, such as chemical incompatibility, covalent bond formation, or degradation-related interactions between mefenamic acid and copovidone. Pharmacokinetic evaluation revealed substantial improvements, including a 2.1-fold increase in Cmax (p < 0.05) and a 1.7-fold increase in AUC₀–∞ (p < 0.05). The reduced Tmax further reflects faster absorption and improved systemic availability. Stability studies confirmed the retention of the amorphous state and dissolution profile throughout the storage period.

Conclusion

Overall, Copovidone-assisted hot-melt extrusion proved to be an efficient strategy for enhancing the solubility, dissolution rate, and oral bioavailability of mefenamic acid. The optimized formulation demonstrates strong potential as a commercially viable platform for developing bioavailability-enhanced oral dosage forms of poorly soluble drugs.

Graphical Abstract