Application of Near-Infrared Spectrometry to Evaluate the Mechanism of Wet Granulation Using a High-Speed Mixer with Porous Calcium Silicate and Sugar Alcohols.

The current study examined the mechanism of wet granulation with a high-speed mixer using porous calcium silicate (PCS) as the excipient and low-molecular-weight sugar alcohols (erythritol, mannitol, maltitol, or xylitol) as the binder. Granules did not form when erythritol or mannitol was used as the binder. No major changes in X-ray powder diffraction data and near-infrared (NIR) spectroscopy spectra were noted when erythritol was used in granulation. Meanwhile, granules formed when xylitol was used as the binder. The NIR spectra of the obtained granules had a widened band near 5100 cm due to hydroxyl groups. From the peak fitting near 4800 cm using the Gaussian-Lorentzian product function, the contribution of hydrogen bonds in water species increased during granulation. The NIR spectra of these potential binders revealed a band of hydroxyl groups for intramolecular hydrogen bonds near 6900 cm when maltitol or xylitol was used as the binder, whereas no band was observed for erythritol and mannitol. Changes in the NIR spectra assigned to water were useful in evaluating the progression of granulation as a process analytical technology. Moreover, X-ray powder diffraction illustrated that the peak due to xylitol crystals disappeared. Xylitol existed in an amorphous state in the granules, suggesting molecular interactions. Thus, hydroxyl groups in sugar alcohols facilitate hydrogen bonding between PCS (silanol groups) and molecules via water, and this is considered to be the mechanism by which granules are formed.