Structure and process relationships in extruded polymer systems: Solid-state remodeling of oxymetazoline

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Hot-melt extrusion (HME) is vital for drug-polymer systems, but traditional preformulation methods struggle with processing conditions.
• Conventional approaches often rely on equilibrium states, which may not accurately predict behavior during dynamic HME processes.

Purpose of the Study:

• To propose and validate a process-informed preformulation strategy for investigating structure-process relationships in HME.
• To evaluate the influence of thermodynamic miscibility versus kinetic and mechanical factors on drug-polymer systems during extrusion.

Main Methods:

• Utilized oxymetazoline hydrochloride (OXY), a thermally sensitive drug, and selected polymers based on Hansen Solubility Parameters (HSP).
• Conducted thermal, solid-state, and rheological characterization of extruded drug-polymer systems.
• Investigated structure-process relationships under realistic melt processing conditions.

Main Results:

• Hansen Solubility Parameters (HSP) offered initial compatibility insights but did not fully predict post-extrusion solid-state outcomes.
• Systems with lower predicted thermodynamic compatibility showed significant structural changes, highlighting the importance of kinetic and mechanical factors.
• Melt viscoelasticity played a key role in energy transfer and drug-polymer interactions during the extrusion process.

Conclusions:

• Thermodynamic predictions alone are insufficient for anticipating solid-state behavior in HME-processed pharmaceutical systems.
• A process-informed approach integrating theoretical and experimental methods is essential for rational drug-polymer system design.
• This framework supports the development of pharmaceutical materials under realistic processing conditions, considering both thermodynamic and kinetic aspects.