PAT SUPPLEMENT


properties of the material at significantly different levels of variables. However, in real pharmaceutical manufacturing, the process will be running at optimised process variables and so PAT analysers need to be designed and validated to quantify very small but critical differences in the properties of the product due to small changes in the manufacturing environment or variables. Various techniques have been utilised and shown to be promising. However, great efforts are required prior to these types of PAT tools being routinely utilised in the pharmaceutical industry. We conducted studies on a twin screw extruder with glipizide


and ibuprofen with polyethylene oxide (PEO) in a similar set up using NIR for in-line monitoring of the drug concentration in extrudates7


.


A good correlation was found between the concentration of glipizide predicted using NIR monitoring and the actual concentration. However, the extrudates of the ibuprofen PEO system were transparent and NIR failed to measure this system. A similar study was conducted by Thermo Fisher Scientific involving ibuprofen and Kollidon on a twin screw extruder using NIR probes for monitoring the ibuprofen concentration8


. This extruded system was


also transparent, resulting again in the failure of NIR as an analytical tool. In this study, the addition of five per cent lactose to add opacity to the system was found to be useful in improving the sensitivity and selectivity, as the system showed good correlation between the predicted and actual drug concentrations. A similar set up of the twin screw extruder equipped with in-line monitoring using NIR probes was utilised to study the novel solvent free continuous cocrystallisation (SFCC) process9


. In this process, the drug and conformers are blended and subjected to extrusion at, or near, to the


“ The calibrations conducted over multiple temperature configurations could not give accurate results ”


melting point of the lower melting component (or the eutectic temperature of the system) to produce cocrystals. As NIR has been reported for monitoring the solid state or polymorphic changes, this system was utilised for monitoring the formation of cocrystals in SFCC using a partial least square analysis. An excellent correlation (correlation coefficient 0.999) was observed between the measured and predicted purity of cocrystals formed when process parameters such as the screw configuration were changed under constant temperature conditions. This method failed, however, to detect the minor changes in the purity of the formed cocrystals with variation in extruder screw rotation speeds. When the processing temperatures were changed, only a reasonable correlation (correlation coefficient 0.903) was observed between the predicted and the actual purity of cocrystals. It is a well known fact that changing the temperature causes changes in the absorption patterns in the NIR region. Therefore, the calibrations conducted over multiple temperature configurations could not give accurate results. Judgements or interpretations should be based on a thorough understanding of the process and analytical methods to be applied. The selectivity and sensitivity of the analytical techniques used as PAT analysers should be tested in


www.europeanpharmaceuticalreview.com


European Pharmaceutical Review Volume 16 | Issue 6 | 2011


Today, many companies are not only striving to manufacture high quality products, but also increase production effi ciency by installing the analytical systems directly into their production plants. This improves process verifi ability and process understanding and gives the company the opportunity to optimize material use, run-time of machines and quality of the products up to real-time-release.


Bruker´s spectroscopical technology based on modern FT spectrometers can be used at a lot of different process steps and offer high amount information to gain better process knowledge. The robust design of all spectrometers enables usage in tough conditions in production plants with very low maintenance costs/ times.


Contact us for more details: www.brukeroptics.com


Bruker Optik GmbH


Rudolf-Plank-Str. 27 D-76275 Ettlingen


Tel: +49 (7243) 504-2000 Fax: +49 (7243) 504-2050 E-Mail: info@brukeroptics.de


Process Analytical Technology


MATRIX-F FT-NIR Spectrometer


Allows in-line measurements e.g. in blender, granulators, dryers, and coaters leading to a better understanding and control of processes.


MATRIX-MF FT-IR Spectrometer


Development/process spectrometer ideal for real-time monitoring and analysis of chemical and biological reactions.


MPA FT-NIR Lab Spectrometer


Modular, multi-channel system for your needs in incoming goods identi- fi cation up to product or content uniformity control.


Innovation with Integrity FT-NIR


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