Application of Online NIR Spectroscopy to Enhance Process Understanding and Enable In-process Control Testing of...

Area of Science:

• Pharmaceutical Manufacturing
• Process Analytical Technology (PAT)
• Spectroscopy

Background:

• Spray drying is a critical process for producing pharmaceutical intermediates.
• Secondary drying requires precise endpoint determination to ensure product quality.
• Traditional off-line testing for residual solvents and assay is time-consuming and labor-intensive.

Purpose of the Study:

• To implement Near Infrared Spectroscopy (NIRS) for real-time monitoring of the secondary drying process.
• To develop NIRS methods for quantifying residual solvents (acetone, water) and API assay in spray-dried intermediates.
• To validate and transfer these NIRS methods to a commercial scale.

Main Methods:

• Utilized Near Infrared Spectroscopy (NIRS) for in-line process monitoring.
• Developed calibration models using Partial Least Squares (PLS) regression.
• Validated NIRS methods for residual solvents and API assay with low Standard Errors of Prediction (SEP).
• Transferred and updated NIRS methods to commercial-scale equipment at a different site.

Main Results:

• Achieved accurate quantification of residual acetone (SEP: 0.1 wt. %), water (SEP: 0.2 wt. %), and API potency (SEP: 3.0 mg API/g SDI).
• Successfully transferred NIRS methods to commercial scale, demonstrating robustness across different instrumentation and sites.
• Enabled real-time, in-process release and improved data consistency by minimizing sample handling.

Conclusions:

• NIRS is a viable technology for real-time monitoring and control of secondary drying in spray-dried intermediates.
• NIRS methods reduce reliance on off-line testing, improving efficiency and data quality.
• These NIRS methods offer potential for optimizing drying cycle times and understanding process parameter impacts.