Quality-by-Design (QbD): Process Trajectory Development for a Pharmaceutical Co- precipitation Process Based on an Integrated Real-Time Process Monitoring Strategy

摘要

Pharmaceutical co-precipitation as an important technique to improve the dissolution and absorption of poorly soluble drugs has been modified to prepare extended release preparations. However, no much attention has been paid to demonstrate the process understanding of this important process. Process knowledge is an essential part of the Quality-by-Design (QbD) design space establishment. In this work, an integrated PAT approach was developed for real-time monitoring of a pharmaceutical (naproxen) and a polymer (eudragit) co-precipitation process. Process trajectory was constructed based on principal component analysis (PCA) of the real-time PAT data, including process NIR spectra and process turbidity data. The process trajectory clearly reveals various distinguishable process events and process signatures, such as incubation, nucleation, and crystal growth. The practical implication of the process knowledge gained for process control and the establishment of operational process space will be discussed.