Thermodynamic Aspects of the Preparation of Amorphous Solid Dispersions of Naringenin with Enhanced Dissolution Rate

Amorphous ternary solid dispersions of poorly water-soluble Naringenin (NRG) in Poloxamer 188 (POX) and Neusilin US2 (NSL) were prepared in a Hot- Melt Extruder (HME) using the principle of Low-Temperature Solubilization. Before HME, the NRG-POX solid-state interaction was investigated using Flory Huggins (F-H) theory. Construction of the composition-phase diagram showed Gibbs free energy to be negative close to the melting temperature of NRG, indicating a miscible system.

Highlights
• Low-temperature solubilization technique is proposed to prepare amorphous ternary solid dispersions of Naringenin using HME.

• The miscibility between Naringenin and Poloxamer was estimated from the interaction parameter χ calculated from the solubility parameter and melting point depression.

• Phase diagrams were constructed for an understanding of miscibility and physical stability.

• The XRD and DSC data were found to be in good agreement with the predicted composition using the phase diagram.

• The release of Naringenin in 2 hours from ternary solid dispersions was found to be 77%, which is an increment of 250% from that of pure Naringenin crystal.

The temperature-composition phase diagram provided insights on the phase behavior of the active-polymer solid dispersion system. The interactions and phase behavior predicted within the framework of the F-H theory were further investigated using Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), Hot Stage Microscopy (HSM) and Fourier-transform infrared spectroscopy (FT-IR). Based on the findings, amorphous solid dispersions of NRG were prepared via HME, which demonstrated a significant increase in the dissolution rate (p ≤ 0.05). The enhancement of the dissolution rate is due to conversion from crystalline to amorphous form, as confirmed by DSC and XRD. The amorphous NRG prepared in the current study exhibited a release of 77 % at the end of 2 hours, which is an increment of 250% from that of pure crystals. Continue on Thermodynamic Aspects of the Preparation of Amorphous Solid Dispersions