Agitation Fluidized Bed Granulation Research Articles

Application of a neural network to granulation scale-up

This paper describes a practical method for granulation scale-up by means of a neural network. Wet granulation was conducted using an agitation fluidized bed, and the scale-up characteristics were investigated using a neural network with back-propagation learning. Granule properties obtained by production-scale granulation under various operating conditions were predicted. Extremely good correlation was obtained between the predicted data and the experimental data of agitation fluidized bed granulation. It was found that granulation scale-up could be conducted with high accuracy by a neural network without constructing a mathematical model with a complicated non-linear relationship using a vast amount of experimental scale-up data.

Preparation of core particles for aqueous film coating using agitation fluidized bed.

Core particles used for aqueous film coating were prepared by agitation fluidized bed granulation, and effect of the damping speed on the granule properties of mass median diameter, geometric standard deviation, apparent density, yield, friability and specific surface area were investigated. Film coating by an aqueous acrylic copolymer (Eudragit NE-30D) was carried out using the core particles granulated under three levels of damping speeds, and the drug release properties of each coated product were identified. Relationship between properties of core particles and the drug release properties were clarified and the optimal granulation conditions to make optimal core particles for film coating were determined.

Optimization and validation of an image processing system in fluidized bed granulation

In a previous paper (Watano et al., Powder Technol. 83, 55–60 (1995)), we developed a particle image probe and an image processing system to continuously monitor granule growth in fluidized bed granulation. This paper describes optimization of the image processing system in agitation fluidized bed granulation. First, the effects of operating parameters of the image processing system (e.g. the sensor location and the number of particles analyzed) on the results of granule measurements were investigated experimentally, and the optimum operating parameters were determined. Secondly, the performance and validity of the optimized system were investigated under various liquid flow rates in actual agitation fluidized bed granulation. It was concluded that the optimized system could measure granule number median diameter and shape factor in fluidized bed granulation with high accuracy under various operating conditions.

Scale-Up of Agitation Fluidized Bed Granulation. V. Effect of Moisture Content on Scale-Up Characteristics.

Characteristics of granulation scale-up with moisture variation were investigated using an agitation fluidized bed of four sizes (vessel diameter 125, 230, 500 and 750 mm). Agitation fluidized bed granulation was done under various levels of moisture content and the vessel sizes. Granule properties of mass median diameter, geometric standard deviation, apparent density, shape factor and friability were investigated to know the effect of moisture content on the scale-up characteristics. It was found that a linear relationship between granule mass median diameter and moisture content was observed regardless of the vessel size, however, the mass median diameter decreased as this size. The geometric standard deviation decreased with increase in moisture content, showing that granule size distribution was narrowed as granule growth progressed; the deviation increased, however, with increase in vessel size. The apparent density and shape factor tended to increase with moisture content and vessel size. It was concluded that these phenomena could be explained by the adhesion and separation force experienced by the granules during granulation. Also, the scale-up characteristics could be well explained by the moisture content.

Scale-Up of Agitation Fluidized Bed Granulation by Neural Network.

Scale-up of wet granulation by agitation fluidized bed was conducted using a hierarchy neural network with a back-propagation learning. Scale-up characteristics of agaitation fluidized bed granulation were self-learned using a developed neural network system, and properties of size, size distribution, apparent density and shape factor of granules prepared by the commercial scale under various operating conditions (moisture content, agitator rotational speed and fluidization air velocity) were predicted. To confirm the method's validity, the predicted properties were compared with the actual granulation data. Good correlation was obtained beteen the predicted and the experimental data of agitation fluidized bed granulation. It was found that the neural network could be a reliable tool to analyze the scale-up characteristics of granulation, and to predict granule properties being produced by the unknown larger scale granulator.

Mathematical Model in the Kinetics of Agitation Fluidized Bed Granulation. Effects of Moisture Content, Damping Speed and Operation Time on Granule Growth Rate.

A population balance equation, in which moisture content was taken into consideration for the coalescence probability of two colliding granules, was proposed to investigate the kinetics of granule growth in agitation fluidized bed granulation. The effects of operating variables such as moisture content, damping speed and operation time on the granule growth and its rate were numerically examined. It was found that the theoretical results intrinsically revealed these effects on granule size, size distribution and granule growth rate. The theory also showed good agreement with the experimental granulation data for pharmaceutical powders. As a result, the granule growth mechanism in agitation fluidized bed granulation was elucidated in detail.

Modeling of Agitation Fluidized Bed Granulation by Random Coalescence Model.

Modeling of agitation fluidized bed granulation was conducted using a proposed random coalescence model, in which adhesion of two colliding particls was judged by the coherent strength of a liquid bridge formed between the particles and the separation force caused mainly by agitator rotation. Properties of coherent strangth and water absorbing characteristics of the starting materials, which were very important to determine granule growth, were also teken into consideration. Granule growth in various powder samples with different properties were simulated and the effects of moisture content and agitator rotational speed on this growth were numerically investigeted. The simulated results were in good agreement with the actual granulation data, and granule growth in various powder samples and operating conditions could be simulated with high accuracy. The mechanism of agitation fluidized bed granulation was also elucidated by the proposed model.

Control of moisture content by adaptive fuzzy control in agitation fluidized bed granulation

This paper describes a novel moisture control system based on the adaptive fuzzy control in agitation fluidized bed granulation. To adjust to the change in the inlet air conditions, a gain scheduling, in which the output gain was regulated depending on the drying capacity of the inlet air, was introduced to a fuzzy control system. Performance of the system was evaluated by the moisture control during granulation at various inlet air temperatures. It was found that remarkable stability, which had been impossible to attain by conventional techniques, was achieved. Based on the results obtained, it was confirmed that the developed system could adjust to the change in the process characteristics without updating the fuzzy rules.

Scale-Up of Agitation Fluidized Bed Granulation. IV. Scale-Up Theory Based on the Kinetic Energy Similarity.

The scale-up theory based on kinetic energy similarity was proposed to elucidate the scale-up characteristics in agitation fluidized bed granulation. In this model, kinetic energy given to granules by agitator rotation and fluidizing air were taken into consideration. It was found that granule mass median diameter, apparent density and shape factor can be well expressed by the parameter (Rω/u)2, which showed the ratio of kinetic energy by agitator rotation to that by fluidizing air. Based on the results obtained, effects of operational variables and scale factor on the granule properties could be explained theoretically and granule growth mechanism in agitation fluidized bed granulation was elucidated in detail.

Scale-Up of Agitation Fluidized Bed Granulation. III. Effects of Powder Feed Weight and Blade Angle on Granule Size, Density and Shape.

This paper presents the experimental results of a study on the scale-up characteristics of granule comopaction and sphericity in an agitation fluidized bed granulation. A pharmaceutical standard formulation was granulated using agitation fluidized bed of three sizes (vessel diameter : 125, 230, 500 mm). The effects of powder feed weight and agitator blade angle on the granule properties of size, density and shape were studied. It was found that granules were compressed and made spherical with an increase in agitator blade angle and vessel scale, while they were not influenced by the powder feed ratio.

Scale-Up of Agitation Fluidized Bed Granulation. I. Preliminary Experimental Approach for Optimization of Process Variables.

Granulation scale-up with an agitation fluidized bed of three sizes (vessel diameter 125, 230, 500 mm) was preliminary investigated. In order to evaluate accurately the scale-up factor on granule properties, process variables such as spray conditions, method for moisture measurement and control, powder feed weight and drying efficiency were optimized.

Computer simulation of agitation fluidized bed granulation by a two-dimensional random addition model.

Computer simulation by a two-dimensional random addition model was proposed to elucidate the mechanisms of granule growth and compaction process of agitation fluidized bed granulation. In this paper, adhesion force by liquid bridge and separation force by agitator rotation were taken into consideration for adhesion probability of colliding granules. Effects of moisture content and agitator rotational speed on granule diameter, shape and internal structure were investigated theoretically. This simulation was applied to actual granulation, in which lactose and corn starch mixed in a weight ratio of 7:3 were granulated by an aqueous solution of hydroxypropylcellulose. Close agreement between simulated and experimental results was obtained.

Scale-Up of Agitation Fluidized Bed Granulation. II. Effects of Scale, Air Flow Velocity and Agitator Rotational Speed on Granule Size, Size Distribution, Density and Shape.

Scale-up characteristics of agitation fluidized bed granulation using a pharmaceutical standard formulation was described. The effects of scale, air flow velocity and agitator rotational speed on granule properties such as granule mass median size, size distribution, apparent density and shape factor were investigated experimentally. Based on the results obtained, the effects of these parameters on granule growth and the mechanism of granule formation in different sized equipment were discussed.

Application of fuzzy logic to bed height control in agitation-fluidized bed granulation

Development of a new technique for producing spherical and well-compacted granules, and the application of fuzzy control to a fluidized bed granulation process are described. An agitation-fluidized bed, a type of fluidized bed equipped with an agitator blade, was used for granulation; bed height was controlled by fuzzy logic based on a linguistic algorithm employing IF—THEN rules, to maintain a constant bed height and impart effective agitation to the granules. It was shown that bed height control was effective in preventing defluidization and channeling, and was necessary for automatic operation. The effects of bed height and agitator rotational speed on granule properties, such as apparent density, and on granule shape were investigated. A new technique is proposed for utilizing bed height control to produce spherical and well-compacted granules, which cannot be done using conventional fluidized bed techniques.