Development and Validation of an in-line API Quantification Method Using AQbD Principles Based on UV-Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process

This paper details the development and validation of an in-line analytical method for quantifying piroxicam, an active pharmaceutical ingredient (API), within Kollidon® VA 64 during a continuous hot melt extrusion (HME) process. The methodology employs UV-Vis spectroscopy, guided by Analytical Quality by Design (AQbD) principles. The study established an analytical target profile (ATP) for piroxicam content and developed a novel in-line analytical procedure using predictive models derived from UV-Vis absorbance spectra. A failure mode and effect analysis (FMEA) was conducted to assess risks to the analytical procedure's consistency. Critical analytical attributes, including color parameters (L* lightness, b* yellow to blue), were measured as in-process critical quality attributes linked to API content and transmittance. Method validation adhered to the accuracy profile strategy and ICH Q2(R1) criteria, demonstrating that 95% β-expectation tolerance limits for all piroxicam concentrations were within ±5% acceptance limits. The method's robustness was confirmed by evaluating the effects of screw speed (150–250 rpm) and feed rate (5–9 g/min) on piroxicam content. In-line UV-Vis spectroscopy proved to be a robust and practical Process Analytical Technology (PAT) tool for real-time monitoring of piroxicam content, a critical quality attribute in pharmaceutical HME.

This paper details the development and validation of an in-line analytical method for quantifying piroxicam, an active pharmaceutical ingredient (API), within Kollidon® VA 64 during a continuous hot melt extrusion (HME) process. The methodology employs UV-Vis spectroscopy, guided by Analytical Quality by Design (AQbD) principles. The study established an analytical target profile (ATP) for piroxicam content and developed a novel in-line analytical procedure using predictive models derived from UV-Vis absorbance spectra. A failure mode and effect analysis (FMEA) was conducted to assess risks to the analytical procedure's consistency. Critical analytical attributes, including color parameters (L lightness, b yellow to blue), were measured as in-process critical quality attributes linked to API content and transmittance. Method validation adhered to the accuracy profile strategy and ICH Q2(R1) criteria, demonstrating that 95% β-expectation tolerance limits for all piroxicam concentrations were within ±5% acceptance limits. The method's robustness was confirmed by evaluating the effects of screw speed (150–250 rpm) and feed rate (5–9 g/min) on piroxicam content. In-line UV-Vis spectroscopy proved to be a robust and practical Process Analytical Technology (PAT) tool for real-time monitoring of piroxicam content, a critical quality attribute in pharmaceutical HME. Research Background and Significance The development of robust and reliable analytical methods for real-time monitoring of active pharmaceutical ingredient (API) content during continuous pharmaceutical manufacturing processes is a critical need driven by regulatory trends and industrial demands. Hot melt extrusion (HME) is a continuous manufacturing technique widely used for producing solid dispersions containing A