Method development and validation of a near-infrared spectroscopic method for in-line API quantification during
Liang Zhong1, Lele Gao1, Lian Li1
1NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.
Summary
Near-infrared spectroscopy (NIRS) effectively monitors active pharmaceutical ingredient (API) content during fluidized granulation. An innovative Extended Iterative Optimization Technique (EIOT) demonstrated superior accuracy for in-line API quantification.
Area of Science:
- Pharmaceutical Technology
- Analytical Chemistry
- Process Analytical Technology (PAT)
Background:
- Active pharmaceutical ingredient (API) quantification is crucial for ensuring drug product quality during fluidized granulation.
- Traditional methods for API content monitoring are often time-consuming and not suitable for real-time process control.
- Near-infrared spectroscopy (NIRS) offers a non-invasive and rapid analytical approach for process monitoring.
Purpose of the Study:
- To develop and validate an in-line NIRS method for monitoring API content uniformity during fluidized bed granulation.
- To evaluate the performance of an innovative Extended Iterative Optimization Technique (EIOT) against conventional chemometric methods.
- To demonstrate the suitability of NIRS for real-time API quantification in pharmaceutical manufacturing.
Main Methods:
- A portable NIRS system was employed for in-line monitoring during fluidized bed granulation.
- The Extended Iterative Optimization Technique (EIOT) was developed and applied for API quantification.
- Principal Component Analysis (PCA) and Partial Least Squares Regression (PLSR) were used for comparative analysis.
- High-Performance Liquid Chromatography (HPLC) was utilized for offline validation of NIRS predictions.
- Raman imaging technology was used to visualize the spatial distribution of API within granules.
Main Results:
- The EIOT method demonstrated high accuracy in predicting API concentration across a range of 75% to 125% of the label claim.
- NIRS method using EIOT showed superior performance compared to PCA and PLSR for API quantification.
- Offline HPLC analysis confirmed the reliability of the NIRS-based EIOT method.
- Raman imaging provided insights into the spatial homogeneity of API distribution in the granules.
Conclusions:
- The developed NIRS method, coupled with EIOT, is a suitable and accurate tool for in-line monitoring of API content during fluidized granulation.
- This approach offers a novel strategy for real-time determination of API content, enhancing process understanding and control.
- The findings support the implementation of NIRS as a Process Analytical Technology (PAT) for pharmaceutical granulation processes.
