FDA
Dilantin
Research Approach: This research project has focused on pilot-scale manufacturing of Dilantin capsules as a CRADA with Pfizer. Initially, the blending of phenytoin sodium with excipients was monitored by on-line near-infrared (NIR) spectroscopy and at-line chemical imaging techniques. Subsequently, on-line monitoring by power consumption, blend temperature and headspace humidity have been implemented. Protocol 1 was designed to test the instrument measurement capabilities and to correlate spectral data to product performance (capsule dissolution). Process variables include blending time, API particle size and I-bar speed. Performance results indicate that capsule dissolution increases with API milling and decreases with I-bar speed and blending time. Monitoring the process by NIR spectroscopy indicates multiple blending processes: rapid (chemical mixing) and slow (physical changes). The physical changes (powder density and API dehydration) appear to correlate with product performance. Protocol 2 was proposed to develop a design space for the process variables, I-bar speed and blending time. The goal is to determine a proper blending endpoint in real time from the spectral data.