Rational Design of Multicomponent Polymeric Systems Based on a Transient Plasticization Window for Hot-Melt Extrusion

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Polymer Chemistry

Background:

• Hot-melt extrusion (HME) offers advantages for drug product manufacturing but faces challenges with thermolabile active pharmaceutical ingredients (APIs) due to high thermal and shear stresses.
• Reducing processing temperatures is crucial, often achieved by tailoring polymeric systems with specific thermal and rheological properties.

Purpose of the Study:

• To develop a strategy for designing polymeric systems with a transient plasticization window.
• To enable lower processing temperatures in hot-melt extrusion (HME) by reducing melt viscosity.
• To ensure the formation of a structurally stable matrix after cooling.

Main Methods:

• Polymer compatibility was assessed using laser microinterferometry.
• Three- and four-component polymeric systems were formulated and processed via hot-melt extrusion.
• Materials were characterized using differential scanning calorimetry, melt rheology, and storage stability tests.

Main Results:

• A four-component system (PVP K-29/32, PEG 400, PEG 1500, HPC EF) was successfully developed for HME at 70 °C.
• The optimized system yielded a homogeneous extrudate with reproducible rheological behavior.
• The solid-state material demonstrated excellent storage stability without cold flow.

Conclusions:

• Effective polymeric system design for HME prioritizes transient viscosity reduction during processing over achieving the lowest glass transition temperature.
• The developed approach facilitates structural stabilization post-extrusion.
• This strategy is applicable for creating polymeric premixes for dosage forms, particularly those containing thermolabile APIs.