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

Ryo Omata,Tomoaki Sakamoto,Tetsuo Sasaki,Yusuke Hattori,Makoto Otsuka

doi:10.3390/ph13090226

Abstract

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.

Highlights

High-speed shear wet granulation (HSWG) is a widely used method as raw granules manufacturing process and is an important manufacturing process for solid oral dosage forms such as tablets in the pharmaceutical industry [1,2]
To clarify the intermolecular interaction between particle and binding water during the HSWG process, the experimental condition was conducted far exceeding the ratio of powder and bound water comparing with real granulation as a model experiment
In the process based on F-2 consisting of a mixture of lactose monohydrate (LA) and potato starch (PS), agitation power consumption (APC) increased with increasing Wa, and it reached the maximum APC value at 17 min (140 mL); it decreased as the Wa increased

Summary

Introduction

High-speed shear wet granulation (HSWG) is a widely used method as raw granules manufacturing process and is an important manufacturing process for solid oral dosage forms such as tablets in the pharmaceutical industry [1,2]. The bonding liquid is poured or sprayed into the mixed raw material powder bed and is stirred by the impeller agitates in the HSWG, and the surface tension of the liquid acts between the powder particles to form granules [3] Many process parameters, such as the speed of rotation of the impeller and chopper, the amount of binder and the timing of its addition, and the agitating time of the wet mass, affect the formulation properties of the pharmaceutical preparations [4]. In the previous study [27], to clarify the intrinsic granulation mechanism of HSWG, the dynamic granulation process of the simplest formulation based on glass beads was measured simultaneously by inline NIRS and APC methods This new combination technique was used to clarify the molecular-level role, such as surface tension of water in the binding solution during the HSWG process, and the intermolecular interactions between powder particles and kneading liquid were analyzed based on both NIRS and APC data by multivariate regression analysis. A new analysis method by combining NIRS and APC was applied to the analysis of the molecular interaction of powder particles and binding water during the HSWG granulation process (Figure 1) for standard tablet formulation additive consisting of water-soluble lactose and water-swellable starch

Methods

Results

Conclusion