Continuous manufacture to meet increased demand during a global pandemic: From bench to pilot scale

During pandemics and global crises, drug shortages become critical as a result of increased demand, shortages in personnel and lockdown restrictions that disrupt the supply chain. The pharmaceutical industry is therefore moving towards continuous manufacturing instead of conventional batch manufacturing involving numerous steps, that normally occur at different sites.

Using Hydroxychloroquine Sulphate (HCQS) as the model drug, SoluplusĀ® as a model polymeric carrier and both small-scale horizontal and vertical twin screw hot melt extrusion extruders, seven formulations were processed at various drug loadings, temperature profiles and screw speeds.

When utilising a horizontal extruder, formulations with the highest drug load and processed at the lowest screw speed and temperature had the highest crystallinity with higher drug release rates. Upon scale-up to a vertical extruder, the crystallinity of the HCQS was significantly reduced, with less variation in both crystallinity and release profile across the different extrudates.

This demonstrates improved robustness with the pilot-scale vertical extruder compared to lab-scale horizontal extruder. The reduced variation with the vertical extruder will allow for short increases in production rate, with minimum impact on the CQAs of the final product enabling high-performance continuous manufacturing with minimum waste of raw materials.

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