Understanding the Impact of Chemical Variability and Calibration Algorithms on Prediction of Solid Fraction of Roller Compacted Ribbons Using Near-Infrared (NIR) Spectroscopy

Abstract

The study is aimed at developing a near-infrared (NIR) method for predicting solid fraction (SF) of dry granulated ribbons manufactured with formulation variability. The study investigated the impact of unmodeled chemical variability and regression approaches on method performance. The study utilized an excipient-only formulation system. Calibration compacts were created with chemical and processing variability; followed by collection of NIR spectra. Partial least squares (PLS) and spectral slope algorithms were utilized to model compact SF. Later, the models were deployed to predict SF of test ribbons and compacts containing an API at various concentrations. The risk associated with unmodeled chemical variation manifested itself through generation of new peaks and decreased baseline absorbance in the NIR spectra. The spectral slope was able to better manage this risk, as demonstrated by relatively higher robustness to the increasing load of the active pharmaceutical ingredient (API). The reduced robustness of the PLS approach was attributed to the impact of chemical variability on both spectral baseline and peak absorbance. A prediction error of approximately 5% was observed at 10% drug load using the spectral slope approach. An understanding of the risk associated with unmodeled variability will enable NIR method development as an API sparing technique for low-dose product development.

A Systematic Review: Exploration of Process Analytical Technology Techniques (Pat) and Their Multifaceted Advantages in Industrial Processes

“…Chemical changes can be detected during stability tests. Polymorph changes, hydration-dehydration exchange, and deformation are all common processes that contribute to the instability of physical complexes [37].…”

Determination of Spatially Resolved Tablet Density and Hardness Using Near-Infrared Chemical Imaging (NIR-CI)

“…Several publications in the past have demonstrated the capability of NIR spectroscopy to model the density of pharmaceutical compacts. [20][21][22][23] Local fracture hardness (local Young's modulus) quantifies the resistance of material towards plastic deformation and measurement of its bulk deformation behavior, which is tested using micro-indentation. 24 A robust understanding of material plasticity is critical to achieve successful design of pharmaceutical formulations, as it impacts manufacturability and common tableting issues.…”