Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

oleh: Steven A. Ross, Andrew P. Hurt, Milan Antonijevic, Nicolaos Bouropoulos, Adam Ward, Pat Basford, Mark McAllister, Dennis Douroumis

Format: Article
Diterbitkan: MDPI AG 2021-03-01

Deskripsi

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.