Review of sensing technologies for measuring powder density variations during pharmaceutical solid dosage form manufacturing

Oral solid dosage forms, the most widely used pharmaceutical products, are typically manufactured through a series of processes that transform a blend of drug and excipient particles into a densified product with consistent quality attributes. While the densification of powder during processing is crucial and directly impacts the quality of the drug product, there is still scarcity of non-destructive and fast sensor systems that provide access to the powder density at critical process stages. This review discusses methods for monitoring density variations of particulate matter by describing their principles and presenting application examples. The techniques discussed range from common in-line methods such as near-infrared spectroscopy, acoustic emission and ultrasonic methods as well as techniques with potential to be more frequently applied in a pharmaceutical manufacturing line, i.e., terahertz spectroscopy and imaging, microwave technique, electrical tomography and X-ray based methods. This review also compares these techniques in terms of measurement and data processing time, resolution and its ability to be integrated in a process.