On-line rheological characterization of semi-solid formulations

摘要

The rheological profile of a semi-solid product is a critical quality attribute. To monitor changes of this attribute during manufacturing, it would be beneficial to measure the rheological parameters in an on-line or in-line mode and implement this as a part of a control strategy for manufacturing of semi-solids. None of the process analytical technology (PAT) tools for measuring the rheological parameters have yet been widely accepted in the pharmaceutical area, as most of the equipment can only measure viscosity. Therefore, an automated system based on the measurement of pressure difference across both a topology optimized channel and a tube geometry (capillary viscometer) was investigated. The Pressure Difference Apparatus (PDA) can sample from the bulk intermediate/product stream and press the sample through the apparatus at different flow rates to yield a frequency sweep (G' and G '') and a flow curve (viscosity). A calibration model was successfully prepared and verified with hydroxyethyl cellulose gels with polymer content varying from 1.0 to 1.5% (w/w) resulting in gels of different viscosities. The calibration model was used on-line during manufacturing of a gel and manufacturing changes related to dilution of the product were clearly reflected in the batch evolution profiles. The measurements with the PDA reflected the shear rate and frequency ranges relevant for manufacturing and thereby complemented the rheology measurements obtained with a standard rheometer with real time data.