Phase transformations of erythromycin A dihydrate during pelletisation and drying

Abstract

An at-line process analytical approach was applied to better understand process-induced transformations of erythromycin dihydrate during pellet manufacture (extrusion–spheronisation and drying process). The pellets contained 50% (w/w) erythromycin dihydrate and 50% (w/w) microcrystalline cellulose, with purified water used as a granulating fluid. To characterise changes in solid-state properties during processing, near infrared (NIR) spectroscopy and X-ray powder diffraction (XRPD) were applied. Samples were taken after every processing step (blending, granulation, extrusion, and spheronisation) and at predetermined intervals during drying at 30 or 60 °C. During pelletisation and drying at 30 °C no changes occurred. Partial transformation to the dehydrated form was observed for the pellets dried at 60 °C by NIR and XRPD. The variable temperature XRPD measurements of the wet pellets (from 25 to 200 °C) also confirmed the change to erythromycin dehydrate at approximately 60 °C.