Scale-up of high shear granulation based on the internal stress measurement

Scale-up of wet granulation in a vertical high shear mixer was conducted. Pharmaceutical excipient powders composed of lactose, cornstarch and micro-crystallinecellulose, and hydroxypropylcellulose as a binder were mixed together and then granulated with purified water under various operating conditions and vessel scales. A novel internal stress measurement system was developed and stress of normal and tangential directions that granules received from the agitator blade during the granulation was continuously measured. The results indicated that granules received stress mainly from the tangential direction, which also showed the largest value near at the vessel wall. The effects of the agitator tip speed and the centrifugal acceleration on the measured stress was investigated. It was found that the tip speed of the agitator blade could be the main factor for the granule growth. The physical properties such as strength, size distribution and compressibility of granules prepared by changing the operating conditions and the vessel scales were evaluated and the scale-up characteristics of high shear granulation were investigated experimentally. The results showed that these physical properties had linear correlations with the tip speed. It was finally concluded that the scale-up of high shear granulation could be well conducted by means of the tip speed of the agitator blade.     

Removal of fine powders from film surface. I. Effect of electrostatic force on the removal efficiency

A novel fine particle removal system composed of a corona-discharge neutralizer, a pulse-jet air unit and an image processing system has been developed. First of all, adhesion force between particle and film was directly measured and effect of electrostatic force on the adhesion force was calculated experimentally and theoretically. The electrostatic force was found to be significant, leading to the suggestion that the countermeasure for the electrostatic force was required to effectively remove fine particles. This system was then applied to the removal of fine particles from surface of a gelatin film used for conventional capsule material. The number of particles removed by the system was calculated by an image processing system and number base removal efficiency was computed with and without the elimination of electrostatic charge by the neutralizer. It was found that the difference between the removal efficiency of particles with elimination of electrostatic charge and that of without the elimination showed linear relationship with the electrostatic adhesion force. The data confirmed the necessity of electrostatic charge elimination for the effective removal of fine particles.     

Determination of optimal formulation for extrusion granulation by compression test of wet kneaded mass

The purpose of this study is to propose the application of a compression test to the determination of an optimal formulation for extrusion granulation. The electric current during extrusion was measured and the characteristics of the wet kneaded mass in the compression test were analyzed under various operating conditions, with different types of extruders and several formulations of kneaded mass. It was found that addition of a binder (HPC-L) to pharmaceutical powders lowered the load of a high-compressing type extruder, since the binder reduced the friction among the wet mass during extrusion. Also, the support stress was found to be proportional to the compression pressure without a binder, although an inflection point appeared on the support stress curve when a binder was present. This inflection point suggested large water retention of the wet kneaded mass, at which the medium of pressure was changed from a discontinuous solid powder to a continuous liquid, and large water retention contributed to the low friction of the wet mass. The friction of the wet kneaded mass and the aptitude of the formulation for extrusion were understood by using the compression test. The compression test is a very useful procedure at the first stage of a formulation study.     

Scale-up of wet kneading in a novel vertical high shear kneader

A novel multi-functional vertical high shear kneader has been developed and its performance in wet kneading has previously been reported [Watano et al., Chem. Pharm. Bull., 50(3), 341-345 (2002)]. In this study, scale-up of wet kneading in the novel vertical high shear kneader was conducted. Pharmaceutical excipients composed of lactose, cornstarch and micro-crystalline cellulose were used as powder samples. Kneading operations were conducted under various operating conditions and three different vessel scales. The dried pellets were then prepared by extruding the wet kneaded masses through a dome-type extruder and their drying by a fluidized bed. The physical properties such as strength and disintegration time of the dried pellets were evaluated. It was found that the properties of the dried pellets and their scale-up characteristics were well expressed by an agitation power per unit vessel volume and dimensionless Froude number.     

Granulation of core particles suitable for film coating by agitation fluidized bed I. Optimum formulation for core particles and development of a novel friability test method

To prepare powdered medicines without bitter taste, film coating is required to cover the surface of core particles. In this study, effect of formulation and operating conditions of agitation fluidized bed on the core particle properties was investigated. In order to prevent breakage of the core particles during coating process, which sometimes causes variation of drug dissolution rate, addition of maltose syrup powder during the formulation process of the core particles was investigated. Also, a method for friability test in which the core particles were subjected to strong impact was proposed to evaluate strength of the core particles. The friability of the core particles determined by this test method correlated well with the actual friability of the particles during the coating process. Based on this result, we confirmed this novel friability test method could predict the core particle endurance during the coating process.     

Numerical simulation of film coating process in a novel rotating fluidized bed

In this study, numerical simulation of film coating process in a novel rotating fluidized bed (RFB) was conducted by using a Discrete Element Method (DEM)-Computational Fluid Dynamics (CFD) coupling model. Particle movements and fluid motions in a centrifugal force field were simulated at three-dimensional cylindrical coordinate, and this model was applied to film coating process. Film coating process in a RFB was numerically analyzed by using a simplified assumption that a particle was coated only when a particle existed within a spray zone. The experiments were also conducted and uniformity of sprayed material was evaluated by investigating color difference of the coated particles. As a result of the numerical simulation, three-dimensional bubble movements and particle circulation could be well simulated. In addition, mass of the sprayed material on a single particle in a RFB could be visualized by using our proposed model. The relationship between distribution of the sprayed material and the coating time was also analyzed. Calculated mass distributions of the sprayed material could be expressed by a normal distribution function, showing qualitative good agreement with the previous studies. Effect of the operating parameters, such as gas velocity and centrifugal acceleration, on the uniformity of the sprayed material was also investigated by both numerical and experimental approaches. Comparison of the coating process in a RFB with that in a conventional fluidized bed was also conducted by the numerical simulation. The result showed that uniformity of the sprayed material was greatly improved in a RFB due to the much smaller circulation time.     

Development of a novel compression tester and rheo-mechanical properties of wet-mass powder. II--Effect of moisture content on the rheo-mechanical properties

In our previous paper [Watano S., et al., Chem. Pharm. Bull., 51(7), 747-750 (2003)], a novel compression tester, which enables the vertical and radial pressure transmission measurement, has been developed and quantitative analysis of rheo-mechanical properties of wet-mass powder prepared by different kneading times was conducted. In this study, the compression test was conducted by using the kneaded wet-mass powders prepared by different moisture contents. Pressure transmission characteristics and rheo-mechanical properties have been investigated to characterize the wet-mass powders. The relationship between these parameters and granule physical properties was also investigated.     

Surface Modification of Al2O3 Fiber with Binary Nanoparticles using a Dry-Mechanical Coating Technique

Integrating materials with different functionalities into a composite material to obtain synergetic properties has generated considerable interest in various scientific and technical fields. In this study, a dry-mechanical coating process was used to fix nanosized Al₂O₃ and CuO particles directly onto the surface of Al₂O₃ fiber substrates by employing high shear and compression forces. The resulting composite materials showed good dispersion and homogeneous distribution of Al₂O₃ and CuO nanoparticles. Important coating parameters, including initial particle loadings and processing times were investigated for their effects on coating characteristics and product properties. The experimental results showed that the product surface area increased with higher nanoparticle loadings. The degree of dispersion and homogenous distribution of Al₂O₃ nanoparticles with CuO nanoparticles increased with the processing time. Additionally, the crystalline phase of raw materials was preserved during the coating process under the conditions studied in this work.     

Development of a novel granular detergent with an interspersion particle comprising an anionic surfactant and a polymeric polycarboxalate

This paper discusses a process for making a novel granular detergent with an interspersion particle comprising an anionic surfactant and a polymeric polycarboxalate. This process contains three steps to develop the interspersion particles with anionic surfactant and polymeric ploycarboxalate. The first step was to form a detergent particle by spray drying of an aqueous detergent slurry comprising anionic surfactant (liner alkyl benzene sulfonate) with the different levels of polymeric polycarboxalate. In the second step, the spray-dried granules were densified and ground by a roll compacter and a grinder. The ground particles were coated by nonionic and zeolite in a vertical batch type high shear mixer (third step). In this study, the feasibility to make better performance of granular detergent was discussed.     

Measurement of physical strength of pharmaceutical extruded pellets

This paper describes a novel and simple method for measuring the physical strength of pharmaceutical pellets prepared by extrusion granulation. Pharmaceutical powders composed of lactose, cornstarch, and microcrystalline cellulose were kneaded with purified water and dry binder (hydroxypropylcellulose), then extruded through a dome-type extrusion granulator. The physical strength of the dried extruded pellets was measured with a novel system: pellets and grinding alumina media were both fed into a ball mill pot and then "grinding degree" was measured as defined by the ground fine powder fraction after being rotated in the pot. The grinding conditions such as grinding time and number of alumina balls were optimized. The measured physical strength and pellet strength measured with a typical strength tester was compared. Quantitative relationships between the strength and the physical properties of the pellets such as friability and disintegration time were also investigated. It was found that the newly developed system could easily and accurately evaluate the physical strength of extruded pellets and could also predict the various physical properties.