Specificity of process analytical tools in the monitoring of multicomponent pharmaceutical powders.

The application of Process Analytical Technologies in pharmaceutical manufacturing has been the subject of many studies. Active pharmaceutical ingredient monitoring in real time throughout the manufacturing process is commonly the target of many such implementations. The tools in place must be sensitive to, and selective of, the parameter(s) to be monitored, i.e. in the case of component quantification, they must respond to the component in question and be robust against all others. In this study, four different ingredients (riboflavin, ferrous fumarate, ginseng, and ascorbic acid) in a multi-component blend were monitored by three different tools (near infrared spectroscopy, laser-induced fluorescence and red-green-blue camera) using a full factorial design. The goal was to develop efficient and robust concentration-reading/prediction models able to assess and monitor component interference. Despite relatively high complexity of the blend studied, the three tools demonstrated reasonable specificity for the tracked ingredients (and showed advantages when combined), taking into account larger acceptance criteria typical of dietary products. In certain cases, some interference might lead to biased predictions, highlighting the importance of good calibration. The tools tested and the methodology proposed has divulged their potential in monitoring these components, despite the complexity of the 31-component blend.

Monitoring the concentration of flowing pharmaceutical powders in a tableting feed frame.

The use of process analytical technology (PAT) tools is increasing steadily in the pharmaceutical industry. Such tools are now located throughout the process. When producing tablets, the tableting step itself may be the ideal moment to assess final product composition. Being the last unit operation in tablet production where the elements are still free flowing, it is relatively straightforward to ascertain the composition of the blend in real time. However, a single probe cannot be expected to monitor the composition of every component of a multicomponent blend. In this study, three PAT tools (light-induced fluorescence spectroscopy, near-infrared spectroscopy and color (RGB) imaging) simultaneously checked the composition of powder blends flowing through the feeding unit (feed frame) of a tablet press. The results demonstrate the potential of these tools in monitoring changes in the concentration of a multicomponent mixture in real time, providing users with means to both scrutinize the process and better understand phenomena occurring inside the feed frame.

Using multiple Process Analytical Technology probes to monitor multivitamin blends in a tableting feed frame.

As Process Analytical Technology (PAT) implementation grows in the pharmaceutical industry, more studies are being performed to evaluate its suitability in new applications and processes within the manufacturing chain. As the last step in tablet production, the compression stage represents a critical phase that ensures product quality. In-line control put in place at this stage has the potential to detect powder blends that are out of specification limits and, thus, help to improve product quality. The objectives of the present project are to quantify the composition of a commercial 31-component multivitamin powder blend in real time on an industrial feed frame, using 3 different PAT tools: light-induced fluorescence spectroscopy, near infrared spectroscopy and red, green and blue color imaging. To do so, the concentrations of 5 components (Beta-Carotene, Riboflavin, Ferrous Fumarate, Ginseng and Ascorbic Acid) were alternately changed and monitored with one or many probes. Transition periods between batches served to quantify different powder flow dynamics with sequential composition step changes. The results showed that 4 out of 5 components, each present in commercially-relevant concentrations, could be monitored by one or more tools. Flow dynamics were measured and found to vary significantly in different powder blends.