Design and Evaluation of β-Cyclodextrin Nanosponges for Enhanced Oral Delivery of Eltrombopag Using a Quality by Design Approach

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 demonstrated nanoscale particle size with narrow size distribution, high drug entrapment efficiency, and a marked improvement in dissolution behavior 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 enhancement in drug solubility, and in vitro dissolution studies indicated sustained and diffusion-controlled drug release. Stability studies confirmed acceptable physicochemical stability of the optimized formulation. Conclusion The QbD-guided development of β-cyclodextrin nanosponges successfully improved the solubility and controlled release of Eltrombopag. This nanosponge-based delivery system offers a promising strategy for enhancing the oral bioavailability of dissolution-limited drugs and minimizing absorption variability associated with dietary interactions.