Search Results (6)

Background: The pharmaceutical industry is shifting from end-product testing towards real-time release testing. This approach is based on the continuous collection of process data and product information, which is finally utilized for the release decision. For continuous direct compression, spectroscopic technologies are preferred due to their short acquisition time and non-destructive nature. Methods: Here, the feasibility of the CIELAB color space was demonstrated for porosity and tensile strength. Five different formulations were processed, varying in particle size and deformation behavior. The compression forces were varied from 3 to 18 kN and the CIELAB color space was measured in-line using a UV/Vis probe implemented in the ejection position of the tablet machine. Results: Increasing the main compression force during tableting decreases the tablet surface roughness and porosity. In addition, the tablet tensile strength increases. These changes affected the reflection behavior of radiation on the tablet surface, resulting in a change in the chroma value C*. These dependencies were utilized for the in-line monitoring of porosity and tensile strength. Linear relations were observed for all formulations as exemplary, indicated by sufficient coefficients of determination and verification runs. Conclusions: Finally, UV/Vis diffuse reflectance spectroscopy in combination with a CIELAB color space transformation was demonstrated to be a suitable real-time release tool. Full article

Background: This study demonstrates the application of the sequential design of experiments (DoE) approach within the quality by design (QbD) framework to optimize extrusion processes through screening, optimization, and robustness testing. Methods: An in-line UV–Vis process analytical technology (PAT) system was successfully employed to monitor critical quality attributes (CQAs) of piroxicam amorphous solid dispersion (ASD) extrusion products, specifically lightness (L*). Results: L* measurement proved highly effective for ensuring the quality and uniformity of ASDs, offering real-time insights into their physical appearance and process stability. Small variations in L* acted as early indicators of processing issues, such as phase separation or bubble formation, enabling timely intervention. This straightforward and rapid technique supports real-time process monitoring and control, allowing automated adjustments to maintain product consistency and quality. By adopting this strategy, manufacturers can minimize variability, reduce waste, and ensure adherence to quality target product profiles (QTPPs). Conclusions: Overall, this study highlights the value of in-line UV–Vis spectroscopy as a PAT tool in hot melt extrusion, enhancing CQA assessment and advancing the efficiency and reliability of ASD manufacturing. Full article

Real-time process metrics are standard for the majority of fermentation-based industries but have not been widely adopted by the wine industry. In this study, replicate fermentations were conducted with temperature as the main process parameter and assessed via in-line Oxidation Reduction Potential (ORP) probes and at-line profiling of phenolics compounds by UV-Vis spectroscopy. The California and Oregon vineyards used in this study displayed consistent vinification outcomes over five vintages and are representative of sites producing faster- and slower-fermenting musts. The selected sites have been previously characterized by fermentation kinetics, elemental profile, phenolics, and sensory analysis. ORP probes were integrated into individual fermentors to record how ORP changed throughout the fermentation process. The ORP profiles generally followed expected trends with deviations revealing previously undetectable process differences between sites and replicates. Site-specific differences were also observed in phenolic and anthocyanin extraction. Elemental composition was also analyzed for each vineyard, revealing distinctive profiles that correlated with the fermentation kinetics and may influence the redox status of these wines. The rapid ORP responses observed related to winemaking decisions and yeast activity suggest ORP is a useful process parameter that should be tracked in addition to Brix, temperature, and phenolics extraction for monitoring fermentations. Full article

To avoid any type of cross-contamination, residue-free production equipment is of utmost importance in the pharmaceutical industry. The equipment cleaning for continuous processes such as hot melt extrusion (HME), which has recently gained popularity in pharmaceutical applications, necessitates extensive manual labour and costs. The present work tackles the HME cleaning issue by investigating two cleaning strategies following the extrusion of polymeric formulations of a hormonal drug and for a sustained release formulation of a poorly soluble drug. First, an in-line quantification by means of UV–Vis spectroscopy was successfully implemented to assess very low active pharmaceutical ingredient (API) concentrations in the extrudates during a cleaning procedure for the first time. Secondly, a novel in-situ solvent-based cleaning approach was developed and its usability was evaluated and compared to a polymer-based cleaning sequence. Comparing the in-line data to typical swab and rinse tests of the process equipment indicated that inaccessible parts of the equipment were still contaminated after the polymer-based cleaning procedure, although no API was detected in the extrudate. Nevertheless, the novel solvent-based cleaning approach proved to be suitable for removing API residue from the majority of problematic equipment parts and can potentially enable a full API cleaning-in-place of a pharmaceutical extruder for the first time. Full article

A key principle of developing a new medicine is that quality should be built in, with a thorough understanding of the product and the manufacturing process supported by appropriate process controls. Quality by design principles that have been established for the development of drug products/substances can equally be applied to the development of analytical procedures. This paper presents the development and validation of a quantitative method to predict the concentration of piroxicam in Kollidon^® VA 64 during hot melt extrusion using analytical quality by design principles. An analytical target profile was established for the piroxicam content and a novel in-line analytical procedure was developed using predictive models based on UV-Vis absorbance spectra collected during hot melt extrusion. Risks that impact the ability of the analytical procedure to measure piroxicam consistently were assessed using failure mode and effect analysis. The critical analytical attributes measured were colour (L* lightness, b* yellow to blue colour parameters—in-process critical quality attributes) that are linked to the ability to measure the API content and transmittance. The method validation was based on the accuracy profile strategy and ICH Q2(R1) validation criteria. The accuracy profile obtained with two validation sets showed that the 95% β-expectation tolerance limits for all piroxicam concentration levels analysed were within the combined trueness and precision acceptance limits set at ±5%. The method robustness was tested by evaluating the effects of screw speed (150–250 rpm) and feed rate (5–9 g/min) on piroxicam content around 15% w/w. In-line UV-Vis spectroscopy was shown to be a robust and practical PAT tool for monitoring the piroxicam content, a critical quality attribute in a pharmaceutical HME process. Full article

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon^® VA64 amorphous solid dispersions. The influence of die temperature, screw speed, solid feed rate and PRX concentration on the critical quality attributes (CQAs) absorbance and lightness of color (L*) of the extrudates was investigated using multivariate tools. Statistical analysis results show interaction effects between concentration and temperature on absorbance and L* values. Solid feed rate has a significant effect on absorbance only and screw speed showed least impact on both responses for the screening design. The optimum HME process conditions were confirmed by 4 independent studies to be 20% w/w of PRX, temperature 140 °C, screw speed 200 rpm and feed rate 6 g/min. The in-line UV-Vis system was used to assess the solubility of PRX in Kollidon^® VA64 by measuring absorbance and L* values from 230 to 700 nm. Oversaturation was observed for PRX concentrations higher than 20% w/w. Oversaturation can be readily identified as it causes scattering in the visible range. This is observed by a shift of the baseline in the visible part of the spectrum. Extrudate samples were analyzed for degradation using off-line High-Performance Liquid Chromatography (HPLC) standard methods. Results from off-line experiments using differential scanning calorimetry (DSC), and X-ray diffraction (XRD) are also presented. Full article