Experimentally Derived Hansen Solubility Parameters as a Screening Tool for the Formulation of Amorphous Solid...

Area of Science:

• Pharmaceutical Science
• Materials Science
• Chemical Engineering

Background:

• Poor aqueous solubility of crystalline active pharmaceutical ingredients (APIs) is a major challenge in drug development.
• Amorphous solid dispersions (ASDs) enhance solubility but face limitations in API loading and release.
• Current methods often rely on time-consuming trial-and-error approaches for ASD formulation.

Purpose of the Study:

• To utilize experimentally derived Hansen solubility parameters (HSP) as a predictive tool for assessing polymer/API compatibility in ASD formulation.
• To enable early-stage, rational design of ASDs with high API loading capacity and improved dissolution.
• To investigate the influence of polymer/API interactions on ASD performance.

Main Methods:

• Determined HSP values for ten polymers and three APIs using experimental solubility screening and HSPiP software.
• Prepared ASDs via hot-melt extrusion guided by HSP-based miscibility predictions.
• Characterized polymer/API interactions using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC).

Main Results:

• A linear relationship was found between relative energy difference (RED) and maximum amorphous API soluble (MADS), with lower RED correlating to higher API loadings (up to 45%).
• Specific intermolecular interactions significantly impacted dissolution behavior, as evidenced by FTIR and DSC.
• Amorphous griseofulvin release increased by up to 235% in ASDs with minimal intermolecular interactions compared to crystalline griseofulvin.

Conclusions:

• Experimentally derived HSP reliably predict ASD miscibility and API loading capacity.
• Physicochemical characterization provides mechanistic insights into dissolution behavior.
• An integrated framework using HSP facilitates the rational design of high-performance ASD formulations.