Synergistic Enhancement of Diosgenin Dissolution and Bioavailability via Ternary Solid Dispersions and Self-Assembled Polymeric Micelles.

PURPOSE: This study aims to optimize the dissolution properties of the poorly soluble drug diosgenin (Dio) using ternary solid dispersions (TSDs) to enhance its bioavailability. Additionally, we characterized the prepared diosgenin ternary solid dispersions (Dio-TSDs), and explored their potential solubilization mechanisms.

METHODS

Based on carrier screening and solubility evaluation, Soluplus was selected as the primary carrier and combined with either PVP VA64 or PEG 2000 to construct Dio ternary solid dispersions using the solvent method. The optimal formulation of Dio-TSDs was selected based on dissolution performance. Characterization, component interaction analysis, and stability assessment were performed using water contact angle measurements, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), and molecular dynamics (MD). Pharmacokinetics was evaluated in Sprague-Dawley rats.

RESULTS

The Dio: Soluplus: PVP VA64 (10:63:27) -TSD (Dio-S-PVP-TSD) and Dio: Soluplus: PEG2000 (10:81:9) -TSD (Dio-S-PEG-TSD) improved Dio dissolution, reaching dissolution rates of 92.24% and 79.69%. Characterization results demonstrated that the carriers improved the wettability of Dio, and Dio was predominantly amorphous in the Dio-TSDs. Spherical-like nanomicelles were observed in aqueous solution. Interaction analysis revealed that non-covalent interactions facilitated the self-assembly of core-shell nanoclusters, with the polymer protecting Dio molecules in the core. Dio-S-PVP-TSD showed better physical stability during storage, whereas Dio-S-PEG-TSD showed a greater ability to maintain supersaturation. Both Dio-S-PVP-TSD and Dio-S-PEG-TSD demonstrated 5.49 and 6.15 times higher bioavailability than pure Dio in pharmacokinetic studies.

CONCLUSION

Dio-S-PVP-TSD and Dio-S-PEG-TSD enhanced the dissolution and bioavailability of Dio, providing a promising strategy for improving the oral bioavailability of poorly soluble compounds.