Scale-Up and In-line Monitoring During Continuous Melt Extrusion of an Amorphous Solid Dispersion

Area of Science:

• Pharmaceutical Technology
• Process Engineering
• Materials Science

Background:

• Chemical degradation during extrusion is a significant challenge for drug substance manufacturing.
• Larger extrusion equipment offers advantages in screw design and operational flexibility.
• Previous work established optimal parameters for meloxicam-copovidone amorphous solid dispersion (ASD) on a smaller extruder.

Purpose of the Study:

• To develop a strategy for scaling up ASD extrusion to an extruder with dissimilar geometry.
• To evaluate the impact of scale-up on the purity of meloxicam-copovidone ASD.
• To investigate the role of meglumine in enhancing stability and solubility.

Main Methods:

• Utilized specific mechanical energy input and degree of fill from a smaller extruder for scale-up.
• Implemented vacuum addition to prevent meloxicam hydrolysis.
• Introduced downstream feeding and micronization to reduce residence time.
• Employed in-line UV monitoring for real-time assessment of meloxicam solubilization.

Main Results:

• Achieved equivalent meloxicam purity (96.7%) on the larger extruder as with the smaller one.
• Successfully maintained high purity with a 20% drug loading by incorporating meglumine.
• Observed solubility enhancement and improved chemical stability of meloxicam with meglumine addition.

Conclusions:

• A viable strategy for scaling ASD extrusion processes to dissimilar equipment was established.
• Meglumine effectively stabilizes meloxicam and enhances its solubility, enabling higher drug loading.
• The developed scale-up approach ensures consistent product quality and purity.