Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation...

Area of Science:

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

Background:

• Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) in amorphous solid dispersions (ASDs).
• ASD preparation involves spraying API-polymer solutions onto excipients in a fluid bed granulator.
• Accurate quantification of API content is essential for process control and product quality.

Purpose of the Study:

• To develop and evaluate spectroscopic methods for quantifying API content during fluidized bed granulation (FBG) for ASD preparation.
• To assess the suitability of Raman and near-infrared (NIR) process analysers for real-time monitoring.
• To investigate the application of partial least squares (PLS) modeling for API quantification.

Main Methods:

• Utilized Raman and three near-infrared (NIR) process analysers.
• Developed four partial least squares (PLS) models using data from multiple granulation batches.
• Assessed model performance using metrics like RMSEP, RMSECV, and RPD.

Main Results:

• Off-line and at-line NIR models demonstrated suitability for process control.
• At-line Raman measurements accurately predicted the spraying phase endpoint.
• PLS models showed good predictability for API content.

Conclusions:

• This is the first study to monitor API content during FBG for ASD preparation using PAT tools.
• Raman and NIR spectroscopy combined with PLS modeling offer novel insights for monitoring and controlling ASD manufacturing.
• The developed methods support real-time quality assessment and process optimization.