Creating a consistent, uniform blend of active ingredients and excipients is a key step in manufacturing pharmaceuticals and other formulations. NIR is, in many cases, an ideal tool for monitoring and controlling blending operations. Most active ingredients have good NIR spectra whilst excipients tend to have weaker spectra which means that blends with relatively low concentrations (>1%) of the active ingredient can be measured. LIF further increases this sensitivity by an order of magnitude.
For low concentrations of actives Raman spectroscopy can also be useful
How it works
Reflectance NIR spectra are collected rapidly during blending – diode array instruments have the necessary speed and sensitivity. The NIR data can be used with a calibration to predict the end point of the blend or, alternatively a calibration-free method can be used. With a calibration for the desired concentration the NIR will report the actual calibration and the blender can be run until the correct concentration is measured by the NIR consistently. Alternatively, the difference between consecutive NIR spectra is calculated as a rolling spectral variance and the blender is run until the NIR response is constant and the mixture is fully blended (see image)
The Prozess Reveal instrument is designed to attach to rotating bin blenders with battery power and wireless communications.(Figure2) The NIR response is measured through a sapphire window, usually located in the lid and a gravity switch triggers data collection when the window is facing downwards and the blend falls onto the window.
High shear and other blenders
direct coupled NIR instruments like the Reveal or other systems with fibre-coupled reflectance probes can be used on almost all types of blender.
Light Induced Fluorescence
LIF can be used as an alternative to NIR when higher sensitivity is required, for high potency pharmaceutical blends for example. Many active ingredients will fluoresce while most excipients do not. The strong distinct fluorescence signal can give sensitivity enhancements and very low concentrations (as low as 0.01% w/w) may be monitored. Like diode array NIR, LIF is also a fast measurement technique.