Elucidation of the Molecular Mechanism of Wet Granulation for Pharmaceutical Standard Formulations in a High-Speed Shear Mixer Using Near-Infrared Spectroscopy.

The granulation process of pharmaceutical standard formulation in a high-speed shear wet granulation (HSWG) was measured by in-line near-infrared spectroscopy (NIRS) and agitation power consumption (APC) methods. The F-1, F-2, and F-3 formulations (500 g) contained 96% w/w α-lactose monohydrate (LA), potato starch (PS), and a LA:PS = 7:3 mixture, respectively, and all the formulations contained 4% w/w hydroxypropyl cellulose. While adding purified water at 10 mL/min, the sample powder was mixed. The calibration models to measure the amount of binding water (Wa) and APC of the HSWG formulations were established based on NIRS of the samples measured for 60 min by partial least-squares regression analysis (PLS). Molecular interaction related to APC between the particle surface and binding liquor was analyzed based on NIRS. The predicted values of Wa and APC for all formulations were superimposed with the measured values on a straight line, respectively. The regression vector (RV) of the calibration model for Wa indicated the chemical information of all the water in the samples. In contrast, the RV for APC suggested that APC changes in the processes are related to powder aggregation because of surface tension of binding water between particles.