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The crystal structures of active pharmaceutical ingredients and excipients should be strictly controlled because they influence pharmaceutical properties of products which cause the change in the quality or the bioavailability of the products. In this study, we investigated the effects of microcrystalline cellulose (MCC) crystallinity on the hydrophilic properties of tablets and the hydrolysis of active pharmaceutical ingredient, acetylsalicylic acid (ASA), inside tablets by using tablets containing 20% MCC as an excipient. Different levels of grinding were applied to MCC prior to tablet formulation, to intentionally cause structural variation in the MCC. The water penetration and moisture absorbability of the tablets increased with decreasing the crystallinity of MCC through higher level of grinding. More importantly, the hydrolysis of ASA inside tablets was also accelerated. These results indicate that the crystallinity of MCC has crucial effects on the pharmaceutical properties of tablets even when the tablets contain a relatively small amount of MCC. Therefore, controlling the crystal structure of excipients is important for controlling product qualities.

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.

Transient water absorption by cellulosic samples manufactured under varying pressure was monitored by near-infrared spectroscopy to explore the absorption behavior affected by the pressure. A substantial level of variation of the spectral features was induced by the water absorption and changes in the pressure. The detail of the spectral changes was analyzed with a multiple-perturbation, two-dimensional (2D) correlation method to determine the underlying mechanism. The 2D correlation spectra indicated that the compression of the cellulose increased the packing density of the samples, preventing the penetration of water. In addition, the compression substantially disintegrated its crystalline structure and eventually resulted in the development of inter- and intrachain hydrogen-bonded structures arising from an interaction between the water and cellulose. Consequently, the cellulose samples essentially underwent an evolutionary change in the polymer structure as well as in the packing density during the compression. This structural change, in turn, led to the seemingly complicated absorption trends, depending on the pressure.

An extension of the two-dimensional (2D) correlation analysis scheme for multi-dimensional perturbation is described. A simple computational form is provided to construct synchronous correlation and disrelation maps for the analysis of microscopic imaging data based on two independent perturbation variables. Sets of time-dependent attenuated total reflection infrared (ATR-IR) spectra of water and cellulose mixtures were collected during the evaporation of water from finely ground cellulose. The system exhibits complex behaviors in response to two independent perturbations, i.e., evaporation time and grinding time. Multiple perturbation 2D analysis reveals a specific difference in the rate of evaporation of water molecules when accompanied by crystallinity changes of cellulose. It identifies subtle differences in the volatility of water, which is related to the crystalline structure of cellulose.