In-process rheometry as a PAT tool for hot melt extrusion

Area of Science:

• Pharmaceutical Technology
• Polymer Science
• Process Engineering

Background:

• Hot melt extrusion (HME) is a key process for pharmaceutical manufacturing.
• Monitoring HME in real-time is crucial for process control and product quality.
• Process Analytical Technology (PAT) aims to improve process understanding and control.

Purpose of the Study:

• To investigate real-time melt rheology measurement as a PAT tool for HME.
• To monitor the influence of active pharmaceutical ingredient (API) loading and temperature on melt properties.
• To assess the sensitivity of rheological parameters to changes in API concentration.

Main Methods:

• Utilized a twin-screw extruder equipped with an instrumented rheological slit die.
• Integrated pressure transducers to measure pressure drop across the die.
• Calculated rheological parameters like shear viscosity and exit pressure at various extrusion throughputs.
• Melted a developmental API with a commercial copolymer at different API loadings and temperatures.

Main Results:

• Observed shear-thinning behavior in the polymer-API melt.
• Melt viscosity decreased with increasing API loading and extrusion temperature.
• Exit pressure and shear viscosity were sensitive indicators of API loading.
• Demonstrated the potential for in-line material attribute measurement.

Conclusions:

• Real-time melt rheology measurement is a viable PAT tool for HME.
• The technique provides valuable insights into API loading and process variations.
• This method can enhance overall process understanding and control in pharmaceutical extrusion.