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Optimizing extrusion processes and understanding conformational changes in itraconazole amorphous solid dispersions
Hetvi Triboandas1, Mariana Bezerra2, Juan Almeida3
1Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK.
International Journal of Pharmaceutics: X
|December 17, 2024
Summary
This study optimized itraconazole (ITZ) amorphous solid dispersions (ASDs) manufacturing using hot-melt extrusion and real-time UV-Vis monitoring. Optimized conditions ensure consistent product quality and demonstrate UV-Vis
Area of Science:
- Pharmaceutical Manufacturing
- Process Analytical Technology (PAT)
- Materials Science
Background:
- Amorphous solid dispersions (ASDs) enhance the bioavailability of poorly soluble drugs like itraconazole (ITZ).
- Hot-melt extrusion (HME) is a key technology for manufacturing ASDs, but requires precise process control.
- Quality by Design (QbD) principles are essential for robust pharmaceutical manufacturing.
Purpose of the Study:
- To optimize the hot-melt extrusion (HME) process for itraconazole (ITZ) amorphous solid dispersions (ASDs) with Kolllidon® VA64 (KVA64).
- To implement and validate in-line UV-Vis spectroscopy for real-time process monitoring and control during ASD manufacturing.
- To establish a design space for the ITZ-KVA64 ASD manufacturing process using a Quality by Design (QbD) approach.
Main Methods:
- Sequential Design of Experiments (DoE) including fractional factorial and central composite designs.
- Hot-melt extrusion (HME) for ASD manufacturing.
- In-line UV-Vis spectroscopy for real-time monitoring of critical process parameters and product attributes.
- Density Functional Theory (DFT) and infrared spectroscopy for conformational analysis.
Main Results:
- Identified ITZ concentration as the most critical process parameter affecting product quality.
- Developed a design space by optimizing feed rate and screw speed, using torque and UV-Vis absorbance as responses.
- Validated robust manufacturing conditions (30% ITZ, 300 rpm, 150°C, 7 g/min) yielding consistent product quality.
- Confirmed UV-Vis spectral shifts correlate with ITZ conformational changes.
Conclusions:
- In-line UV-Vis spectroscopy is a powerful tool for real-time monitoring and control in ITZ-KVA64 ASD manufacturing.
- The QbD approach successfully optimized the HME process, ensuring robustness and consistent product quality.
- Understanding ITZ conformational changes provides critical insights for ASD production and quality control.
Keywords:
Amorphous Solid Dispersion (ASD)Density Functional Theory (DFT)Design of Experiments (DoE)Hot-Melt Extrusion (HME)Itraconazole (ITZ)Quality by Design (QbD), In-line UV–Vis spectroscopyMore Related Videos
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