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Purpose <p>Agomelatine (AG) is an orally administered antidepressant characterized by poor water solubility and extensive hepatic metabolism, resulting in low oral bioavailability. This study aimed to develop agomelatine-liquisolid (AG-LSD) oral disintegrating tablets (ODTs) to enhance drug dissolution and bioavailability.</p> Methods <p>AG was incorporated into a liquisolid system by dissolving the drug in a hydrophilic liquid vehicle and converting it into a dry, free-flowing, and compressible powder using suitable carrier and coating materials. The selected liquisolid formulation was physicochemically characterized and compressed into ODTs using either a natural or a synthetic superdisintegrant. The selected ODT formulation, exhibiting the shortest disintegration and wetting times, was further evaluated through <i>in vitro</i> drug release and <i>in vivo</i> studies and compared with the marketed formulation.</p> Results <p>Propylene glycol was identified as the most effective non-volatile solvent, while the liquisolid formulation containing Avicel PH102 and Aerosil 200 at a carrier-to-coating ratio of 20 exhibited superior flow properties and was selected for ODT preparation. FTIR analysis confirmed the compatibility of AG with the excipients, whereas PXRD, DSC, and SEM analyses indicated the absence of crystalline AG. All prepared ODTs complied with USP specifications. The selected formulation (ODT2) showed a disintegration time of 69.01 ± 3.69&#xa0;s, a wetting time of 20.11 ± 2.67&#xa0;s, and released 81.1 ± 3.2% of AG within 10&#xa0;min. <i>In vivo</i> pharmacokinetic evaluation revealed a 2.64-fold increase in relative bioavailability (RB) compared to the marketed tablets.</p> Conclusion <p>AG–LSD ODTs formulated with natural superdisintegrants represent a promising approach for rapid drug release and significantly enhanced oral bioavailability compared with the marketed AG tablets.</p>

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Formulation and Evaluation of Liquisolid Orally Disintegrating Tablets of Agomelatine with Natural Excipients for Enhanced Oral Bioavailability

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Mohamed S. Mohamed,
  • Koki Ogawa,
  • Reda A. Mahmoud,
  • Abd El hakim Ramadan,
  • Reham A. Abd Elkarim,
  • Ahmed A. El-Shenawy,
  • Tetsuya Ozeki

摘要

Purpose

Agomelatine (AG) is an orally administered antidepressant characterized by poor water solubility and extensive hepatic metabolism, resulting in low oral bioavailability. This study aimed to develop agomelatine-liquisolid (AG-LSD) oral disintegrating tablets (ODTs) to enhance drug dissolution and bioavailability.

Methods

AG was incorporated into a liquisolid system by dissolving the drug in a hydrophilic liquid vehicle and converting it into a dry, free-flowing, and compressible powder using suitable carrier and coating materials. The selected liquisolid formulation was physicochemically characterized and compressed into ODTs using either a natural or a synthetic superdisintegrant. The selected ODT formulation, exhibiting the shortest disintegration and wetting times, was further evaluated through in vitro drug release and in vivo studies and compared with the marketed formulation.

Results

Propylene glycol was identified as the most effective non-volatile solvent, while the liquisolid formulation containing Avicel PH102 and Aerosil 200 at a carrier-to-coating ratio of 20 exhibited superior flow properties and was selected for ODT preparation. FTIR analysis confirmed the compatibility of AG with the excipients, whereas PXRD, DSC, and SEM analyses indicated the absence of crystalline AG. All prepared ODTs complied with USP specifications. The selected formulation (ODT2) showed a disintegration time of 69.01 ± 3.69 s, a wetting time of 20.11 ± 2.67 s, and released 81.1 ± 3.2% of AG within 10 min. In vivo pharmacokinetic evaluation revealed a 2.64-fold increase in relative bioavailability (RB) compared to the marketed tablets.

Conclusion

AG–LSD ODTs formulated with natural superdisintegrants represent a promising approach for rapid drug release and significantly enhanced oral bioavailability compared with the marketed AG tablets.