Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

Steven A Ross; Andrew P Hurt; Milan Antonijevic; Nicolaos Bouropoulos; Adam Ward; Pat Basford; Mark McAllister; Dennis Douroumis

doi:10.3390/pharmaceutics13030419

Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

Pharmaceutics. 2021 Mar 20;13(3):419. doi: 10.3390/pharmaceutics13030419.

Authors

Steven A Ross¹, Andrew P Hurt¹, Milan Antonijevic¹, Nicolaos Bouropoulos^{2

3}, Adam Ward⁴, Pat Basford⁵, Mark McAllister⁵, Dennis Douroumis¹

Affiliations

¹ Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
² Department of Materials Science, University of Patras, Rio, 26504 Patras, Greece.
³ Foundation for Research and Technology Hellas, Institute of Chemical Engineering and High Temperature, Chemical Processes, 26504 Patras, Greece.
⁴ Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, West Yorkshire HD1 3DH, UK.
⁵ Pfizer Global Research & Development, Ramsgate Road, Sandwich CT13 9NJ, UK.

Abstract

The aim of the study was the manufacturing and scale-up of theophylline-nicotinamide (THL-NIC) pharmaceutical cocrystals processed by hot-melt extrusion (HME). The barrel temperature profile, feed rate and screw speed were found to be the critical processing parameters with a residence time of approximately 47 s for the scaled-up batches. Physicochemical characterization using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction of bulk and extruded materials revealed the formation of high purity cocrystals (98.6%). The quality of THL-NIC remained unchanged under accelerated stability conditions.

Keywords: Rietveld refinement; X-ray; cocrystals; continuous manufacturing; hot-melt extrusion; scale-up; solubility; stability; surface dissolution imaging.