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Purpose <p>Eltrombopag is an orally active thrombopoietin receptor agonist whose clinical performance is limited by poor aqueous solubility and variable gastrointestinal absorption caused by chelation with dietary cations. The present study was undertaken to develop and optimize β-cyclodextrin-based nanosponge carriers to improve the solubility, dissolution behavior, and oral delivery of Eltrombopag using a systematic Quality by Design (QbD) approach.</p> Methods <p>β-Cyclodextrin nanosponges loaded with Eltrombopag were prepared using different cross-linking agents and optimized through a Taguchi L9 experimental design. The effects of formulation and process variables on critical quality attributes, including particle size, drug entrapment efficiency, and in vitro drug release, were systematically investigated. The optimized formulation was characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy, phase-solubility analysis, and in vitro dissolution studies.</p> Results <p>The optimized nanosponge formulation (F7) demonstrated a mean particle size of 195 ± 8&#xa0;nm with a polydispersity index of 0.18 ± 0.02, a drug entrapment efficiency of 78.2 ± 1.4%, and a cumulative drug release of 99% at 12&#xa0;h. A marked improvement in dissolution behavior was confirmed compared to the pure drug. Compatibility studies confirmed the absence of chemical interaction between Eltrombopag and formulation excipients, while morphological evaluation revealed a porous nanosponge architecture conducive to drug encapsulation. Phase-solubility analysis showed a linear AL-type enhancement in drug solubility (R² = 0.9998, <i>p</i> &lt; 0.0001), and in vitro dissolution studies indicated sustained and diffusion-controlled drug release consistent with the Higuchi model (R² = 0.987). This work did not carry out any formal stability studies and is advised to be carried out as a future work.</p> Conclusion <p>The QbD-guided development of β-cyclodextrin nanosponges successfully improved the in vitro dissolution and controlled release of Eltrombopag. This nanosponge-based delivery system represents a promising platform for addressing the solubility and dissolution limitations of Eltrombopag. In vitro findings suggest potential for improved oral absorption; however, in vivo pharmacokinetic validation is required to confirm bioavailability enhancement.</p>

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Development and In Vitro Evaluation of β-Cyclodextrin Nanosponges for Improved Dissolution of Eltrombopag: A Quality by Design Approach

  • 期刊论文

  • 发表日期：

    2026年5月9日

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  • Amol R. Pawar,
  • Nidhi P. Shah,
  • Ujashkumar Shah

摘要

Purpose

Eltrombopag is an orally active thrombopoietin receptor agonist whose clinical performance is limited by poor aqueous solubility and variable gastrointestinal absorption caused by chelation with dietary cations. The present study was undertaken to develop and optimize β-cyclodextrin-based nanosponge carriers to improve the solubility, dissolution behavior, and oral delivery of Eltrombopag using a systematic Quality by Design (QbD) approach.

Methods

β-Cyclodextrin nanosponges loaded with Eltrombopag were prepared using different cross-linking agents and optimized through a Taguchi L9 experimental design. The effects of formulation and process variables on critical quality attributes, including particle size, drug entrapment efficiency, and in vitro drug release, were systematically investigated. The optimized formulation was characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy, phase-solubility analysis, and in vitro dissolution studies.

Results

The optimized nanosponge formulation (F7) demonstrated a mean particle size of 195 ± 8 nm with a polydispersity index of 0.18 ± 0.02, a drug entrapment efficiency of 78.2 ± 1.4%, and a cumulative drug release of 99% at 12 h. A marked improvement in dissolution behavior was confirmed compared to the pure drug. Compatibility studies confirmed the absence of chemical interaction between Eltrombopag and formulation excipients, while morphological evaluation revealed a porous nanosponge architecture conducive to drug encapsulation. Phase-solubility analysis showed a linear AL-type enhancement in drug solubility (R² = 0.9998, p < 0.0001), and in vitro dissolution studies indicated sustained and diffusion-controlled drug release consistent with the Higuchi model (R² = 0.987). This work did not carry out any formal stability studies and is advised to be carried out as a future work.

Conclusion

The QbD-guided development of β-cyclodextrin nanosponges successfully improved the in vitro dissolution and controlled release of Eltrombopag. This nanosponge-based delivery system represents a promising platform for addressing the solubility and dissolution limitations of Eltrombopag. In vitro findings suggest potential for improved oral absorption; however, in vivo pharmacokinetic validation is required to confirm bioavailability enhancement.