PHARMACEUTICAL PRODUCTION

In-Line UV/Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

This paper explores the use of an in-line PAT system in pharmaceutical continuous manufacturing using Hot Melt Extrusion (HME) and UV–Vis spectroscopy within a QbD framework. The study, employing a sequential DoE, investigates the effects of process parameters on critical quality attributes for Piroxicam - Kollidon® VA64 dispersions. Statistical analysis revealed interaction effects, with solid feed rate significantly affecting absorbance. Optimal extrusion conditions are determined as 20% w/w PRX, 140 °C temperature, 200 rpm screw speed, and 6 g/min feed rate. In-line UV/Vis can detect drug oversaturation (>20% w/w).

UV/Vis spectroscopy as an in-line monitoring tool for tablet content uniformity

This study focuses on in-line UV/Vis spectroscopy for real-time monitoring of API content in tablets during continuous manufacturing.

The experiments, conducted on a rotary tablet press, involved tablets with theophylline monohydrate (7–13 wt%), lactose monohydrate, and magnesium stearate. The UV/Vis probe, positioned at the ejection point, measured the tablet sidewall. Validation, following ICH Q2 guidelines, confirmed specificity, sufficient linearity (coefficients of determination: 0.9891 for low throughput, 0.9936 for high throughput), and acceptable repeatability (max 6.46%) and intermediate precision (max 6.34%).

UV–VIS spectra as potential process analytical technology (PAT) for measuring the density of compressed materials: Evaluation of the CIELAB color space

This paper presents a novel method using UV/Vis spectrophotometry to determine the density of sample compacts, a critical quality attribute in material processing. By analyzing visible range spectra, color information was calculated and found to be directly proportional to compact density. Comparison with PLS regression showed both methods predicted density with identical accuracy. The direct correlation of color information with density, as an output parameter, required no extensive data pre-processing, making it a potentially efficient process analytical technology tool for implementing into compression processes such as tableting or roller compaction.

Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion

This study addresses pharmaceutical equipment cleaning challenges in hot melt extrusion (HME). Two cleaning approaches are explored after processing polymeric formulations of hormonal and poorly soluble drugs. In-line UV–Vis spectroscopy quantifies very low API concentrations during cleaning, and a novel solvent-based method was developed and compared to a polymer-based one. Results showed the solvent-based approach effectively removes API residue from most equipment areas, suggesting its potential for comprehensive API cleaning-in-place for pharmaceutical extruders.

INNOVATIVE, EASY, AND FAST RESIDENCE TIME DETERMINATION

• • Very short measurement interval of 500 ms
• • Detection of residence time significantly faster and less cumbersome than old methods
• • Simpler and faster than off-line chromatography or the "ash" method
• • Enabled by ColVisTec's ReTA software

IN-SITU RESIDENCE TIME DETERMINATION

• • For HME, a coloured tracer or API can be used to observe mixing, dissolution kinetics and residence time
• • Instantly observe the impact of changing screw speed, feed-rates and temperature gradients
• • Measure API and polymer thermal stability and degradation kinetics
• • Timeframe of the inline measurements including data analysis: few Minutes; timeframe of the chromatography measurements including data analysis: approximately 14 days.