Physicochemical changes and chemical degradation of gliclazide during twin-screw melt granulation.

Using a miscible model formulation consisting of 80% gliclazide (GLZ) and 20% hydroxypropyl cellulose, we investigate how the twin-screw melt granulation process affects the chemical stability and process-induced physicochemical changes of the drug. No degradation was observed in the conveying section that leads to kneading element. Approximately 1/3 of the GLZ degradant was generated at the kneading section, while the remaining 2/3 was generated in the conveying section post-kneading and during cooling outside the barrel. A strong correlation was observed between the overall degradation and the temperature of the granules at the barrel exit. In the kneading section, the degradant content correlates best with the specific mechanical energy. With higher specific mechanical energies, the size of the GLZ crystals was reduced further, resulting in more surface defects. In the section post-kneading element, GLZ degradation correlates best with the granule temperature measured at the kneading section. This knowledge of drug degradation during twin-screw melt granulation can be used to develop processing strategies to maintain drug stability during and post processing.