Granulation of core particles suitable for film coating by agitation fluidized bed III. Effect of scale, agitator rotational speed and blade shape on granule properties and development of a high accuracy scale-up theory.

The preparation of core particles suitable for subsequent film coating was examined using different scales of agitation fluidized beds. Specifically, the effects of agitator rotational speed and agitator blade shape in different scales of granulators on granule properties such as mass median diameter, apparent density, friability and shape factor were studied. As the agitator rotational speed was increased or when the agitator blade height and angle were large, the mass median diameter and friability of the granules decreased, while the apparent density and shape factor increased, in a manner independent of the vessel size because the granules were subjected to greater compression, shearing and rolling effects. The same core particles could not be prepared using granulators with different vessel sizes by simply adopting a conventional scale-up theory(1,2)) based on kinetic energy similarity. Here, a novel scale-up theory that takes into account agitator blade shape factors is proposed.(3)) When the two scale-up theories were compared, our new theory was capable of predicting the granule properties more accurately than the conventional theory. By adopting this novel theory, the same core particles could be prepared under different operating conditions in any scale of granulator.

Granulation of core particles suitable for film coating by agitation fluidized bed II. A proposal of a rapid dissolution test for evaluation of bitter taste of ibuprofen.

To prepare powdered drugs that do not have a bitter taste, a film coating covering the surfaces of the core particles is required. The dissolution rate of ibuprofen from the coated particles changes according to the physical properties of the core particles. In this study, the effects of the physical properties of granules prepared by using several scales of agitation fluidized beds on the drug dissolution rate were investigated. The dissolution rate of ibuprofen decreased when the apparent density and shape factor of the granules increased. In contrast, the dissolution rate of the drug increased with the friablility of the granules increased. Thus, the structures of the granules appear to affect the dissolution rate of the drug to a large degree. A rapid dissolution test that can be used to investigate the early dissolution rate of ibuprofen in vitro was proposed to evaluate the taste-masking level of the coated particles. The bitter taste-masking level of the coated particles was successfully confirmed by using this novel test method.

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.

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.