In this study, we investigated molecular-level variation of tablets caused by grinding and its effect on their actual moisture absorbability. Model tablets contained acetaminophen as an active pharmaceutical ingredient and microcrystalline cellulose (MCC) as an excipient. Different levels of grinding were applied during the tablet formulation to intentionally cause the structural variation of the MCC. The moisture absorbability of tablets showed obvious variation depending on the grinding time, and the corresponding change in near-infrared spectra was readily captured. The detailed analysis of the variation of the band frequencies (i.e., wavenumber) revealed that the grinding process substantially disintegrates the crystalline and generates a glassy amorphous structure of MCC, which is a requirement to absorb water molecules. Consequently, it is very likely that the change of the moisture absorbability of the tablets is closely related to the development of the amorphous structure. These results indicate that the pharmaceutical product performances can be influenced by the physical properties of the excipient, which in turn can be controlled by the grinding process.
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