Process monitoring and evaluation of a continuous pharmaceutical twin-screw granulation and drying process using multivariate data analysis.

The present study aims at acquiring an in-depth process knowledge about a twin-screw granulation and fluid bed drying process performed on the commercially available continuous line. Batch Statistical Process Monitoring (BSPM) principles are used to describe and monitor the variables with a relevant time-related trajectory. The continuous granulator operates in a truly continuous manner and variables logged by this unit do not present time-relevant features. On the other hand, the fluid bed dryer is divided in six identical cells, which are sequentially filled and discharged, ensuring a continuous flow of material. Multiple variables logged at the dryer and subsequent product control unit, present time-relevant features. A profound analysis of these variables logged during normal operation, as well as an in-depth description of the startup period of the different units, were achieved. The BSPM concepts allows to monitor the time relevant variables of this continuous manufacturing line, to detect and diagnose deviations from normal operation and assign possible causes for the disturbances.

Multivariate statistical process control of a continuous pharmaceutical twin-screw granulation and fluid bed drying process.

A multivariate statistical process control (MSPC) strategy was developed for the monitoring of the ConsiGma™-25 continuous tablet manufacturing line. Thirty-five logged variables encompassing three major units, being a twin screw high shear granulator, a fluid bed dryer and a product control unit, were used to monitor the process. The MSPC strategy was based on principal component analysis of data acquired under normal operating conditions using a series of four process runs. Runs with imposed disturbances in the dryer air flow and temperature, in the granulator barrel temperature, speed and liquid mass flow and in the powder dosing unit mass flow were utilized to evaluate the model's monitoring performance. The impact of the imposed deviations to the process continuity was also evaluated using Hotelling's T2 and Q residuals statistics control charts. The influence of the individual process variables was assessed by analyzing contribution plots at specific time points. Results show that the imposed disturbances were all detected in both control charts. Overall, the MSPC strategy was successfully developed and applied. Additionally, deviations not associated with the imposed changes were detected, mainly in the granulator barrel temperature control.

Physicochemical fingerprinting of thermal waters of Beira Interior region of Portugal.

Mineral natural waters and spas have been used for therapeutic purposes for centuries, with Portugal being a very rich country in thermal waters and spas that are mainly distributed by northern and central regions where Beira Interior region is located. The use of thermal waters for therapeutic purposes has always been aroused a continuous interest, being dependent on physicochemical fingerprinting of this type of waters the indication for a treatment in a specific pathological condition. In the present work, besides a literature review about the physicochemical composition of the thermal waters of the Beira Interior region and its therapeutic indications, it was carried out an exhaustive multivariate analysis-principal component analysis and cluster analysis-to assess the correlation between different physicochemical parameters and the therapeutic indications claims described for these spas and thermal waters. These statistical methods used for data analysis enables classification of thermal waters compositions into different groups, regarding to the different variable selected, making possible an interpretation of variables affecting water compositions. Actually, Monfortinho and Longroiva are clearly quite different of the others, and Cró and Fonte Santa de Almeida appear together in all analysis, suggesting a strong resemblance between these waters. Thereafter, the results obtained allow us to demonstrate the role of major components of the studied thermal waters on a particular therapeutic purpose/indication and hence based on compositional and physicochemical properties partially explain their therapeutic qualities and beneficial effects on human health. This classification agreed with the results obtained for the therapeutic indications approved by the Portuguese National Health Authority and proved to be a valuable tool for the regional typology of mineral medicinal waters, constituting an important guide of the therapeutic armamentarium for well and specific-oriented pathological disturbs.

Bioreactor monitoring with spectroscopy and chemometrics: a review.

Biotechnological processes are crucial to the development of any economy striving to ensure a relevant position in future markets. The cultivation of microorganisms in bioreactors is one of the most important unit operations of biotechnological processes, and real-time monitoring of bioreactors is essential for effective bioprocess control. In this review, published material on the potential application of different spectroscopic techniques for bioreactor monitoring is critically discussed, with particular emphasis on optical fiber technology, reported for in situ bioprocess monitoring. Application examples are presented by spectroscopy type, specifically focusing on ultraviolet-visible, near-infrared, mid-infrared, Raman, and fluorescence spectroscopy. The spectra acquisition devices available and the major advantages and disadvantages of each spectroscopy are discussed. The type of information contained in the spectra and the available chemometric methods for extracting that information are also addressed, including wavelength selection, spectra pre-processing, principal component analysis, and partial least-squares. Sample handling techniques (flow and sequential injection analysis) that include transport to spectroscopic sensors for ex-situ on-line monitoring are not covered in this review.