Why some FT-IR peaks disappear in drug-loaded nanocarriers, polymers, and formulated granules? Unmasking the invisible and the role of AI in spectral interpretation

Fourier Transform Infrared (FT-IR) spectroscopy is a cornerstone for verifying drug loading in nanocarriers, polymeric matrices, and formulated granules. However, researchers frequently encounter the disappearance of characteristic drug peaks in the composite spectra, often leading to misinterpretations regarding loading success. This paper critically examines the physicochemical mechanisms behind this phenomenon, including signal masking by dominant substrate bands, crystalline-to-amorphous transitions, and deep encapsulation beyond the penetration depth of ATR-FT-IR. We propose a paradigm shift in spectral interpretation: the absence of discrete drug peaks does not imply loading failure; rather, subtle alterations in the substrate's spectral signature such as shifts, broadening, or intensity variations might serve as proxies for successful functionalization.