A novel system has been developed to continuously monitor granule growth in a high shear granulation. The system consists of an image processing system and a particle image probe comprising a CCD camera, lighting unit and air purge system. Segregation during powder mixing was investigated experimentally and the optimal positioning of the probe was determined. High shear granulation was conducted using pharmaceutical powders, and granule size and product's yield of various size ranges were continuously measured by the developed system. Sieve analysis of the granulated products sampled out during the granulation was simultaneously conducted, and the obtained data was compared with that by the on-line image processing system. An extremely close relationship could be found between both data, proving that the developed system could monitor the granule growth accurately and continuously throughout the granulation. An on-off control system was developed to control the granulation process, and the performance of the system was confirmed.

No abstract

Kneading of powder materials [1][2][3] has been well used in the pharmaceutical, agriculture, food, chemical, forage and fertilizer industries. Most of the cases, kneading operation is conducted just before the extrusion or molding processes, and the performance of kneading seriously affects quality of the final product or process efficiency. Therefore, it is important to quantitatively analyze and monitor the kneading process.So far, a high shear mixer has been well used for wet granulation 4) as well as for wet kneading. In the case that the high shear mixer is used for wet kneading, several advantageous points such as easy to disassemble with easy cleaning can be pointed out. However, the problems such as enormous sticking on the vessel wall or larger physical strength of extruded pellets that may cause longer dissolution time have also been known on the contrary. It is required to improve the problems of high shear mixer while keeping the advantageous points when applied to wet kneading.In this study, a multi-functional vertical high shear kneader has been newly developed and applied for wet kneading. Wet kneading of pharmaceutical powders composed of acetaminophen and excipients was conducted under various blade components and operating conditions. Dispersion of aqueous binder and compression properties of wet mass was investigated to quantitatively analyze the kneading condition. Dried pellets were then produced through a dome type extrusion granulator and a fluidized bed drier, and physical properties of the pellets were examined experimentally.Comparison between kneading performance of the novel kneader and of a conventional high shear mixer (granulator) was also conducted. ExperimentalApparatus Figure 1 shows a schematic diagram of multi-functional vertical high shear kneader (SPG-10, Fuji Paudal Co., Ltd.) developed. The vessel is a laboratory size, which has an inner diameter of 290 mm and a capacity of 10 l. The bottom of the vessel is equipped with a kneading blade that rotates horizontally. Several operating parameters such as torque of main shaft, power consumption of motor drive and temperature of kneaded mass can be continuously measured and monitored via a personal computer. Chopper blade can also be installed onto the sidewall of the vessel, if necessary. Figure 2 illustrates a newly developed kneading blade, and Fig. 3 shows appearance of various blades used. The kneading blade is composed of four parts; (a) scraper, (b) main blade, (c) dispersion blade, and (d) cap. The main blade has an edge having inclination of 20 degrees to the backward, opposite direction of the blade movement. This is designed so as to press down the wet kneaded mass, and to add high compaction force and high shear stress to the mass (typically, main agitator blade of high shear mixer (granulator) has an edge to the opposite direction of our kneading blade, thus powders are lifted up by the edge inclination). The dispersion blade equipped on the top of the main blade works to move away the wet mass to the vessel outsid...

In our previous paper [Watano S., et al., Chem. Phram. Bull., 49(1), 64-68, (2001)], a compaction tester was developed to quantitatively evaluate the water dispersion condition of wet kneaded masses prepared by a paddle type kneader. It was also demonstrated that the physical properties of pellets prepared by extrusion granulation after the kneading could be well predicted by the vertical pressure transmission obtained through the compaction tester. However, in this compression tester, the vertical pressure transmission was just obtained and rheological and mechanical properties (so called rheo-mechanical properties) of wet mass-powder that should be the most important to determine the deformation process were not well studied. In this study, a novel compression tester, which can measure both vertical and radial pressure transmissions, has been developed. Based on the compression test, mechanical property (Young's modulus) and rheological property (effective internal friction) of wet mass powder prepared by different kneading times were quantitatively investigated. Granules (pellets) were then obtained through the extrusion granulation and fluidized bed drying, and the physical properties (strength and disintegration time) of the obtained pellet were evaluated. The relationship between the granule (pellet) physical properties and the mechanical and rheological (rheo-mechanical) properties was analyzed.

No abstract