An accurate detection of micro-collapse during the lyophilization of a 5% w/v lactose solution using a combination of intelligent laser speckle imaging and through-vial impedance spectroscopy

In a freeze drying (FD) process, an accurate observation and control of the process parameters at critical stages are at high importance. Particularly accurate and timely identification of the critical temperature (Tc) at the end of primary drying phase would lead to heating energy cost reduction and product waste elimination by ending the process before the product’s micro-collapse stage. Aim: Within this work, a combination of novel techniques, optical technique called Intelligent Laser Speckle Imaging (ILSI) in association with product image texture analysis, coupled to an electrical impedance technique called through vial impedance spectroscopy (TVIS) has been applied onto the real-time product states observation process to identify the specific structural product surface/subsurface characteristics and hence the micro-collapse stage. Method: 2 cycles – one providing a profile for standard approach (non-collapsed) and another with a temperature ramp through Tc to micro-collapse, TVIS provides an assessment of the onset of micro-collapse through the assessment of the acceleration in drying rate whereas the ILSI with pattern recognition detects the change in microstructure