Chem. Pharm. Bull. 55(8) 1169—1174 (2007)

successful medical treatment, and one of the effective methods to improve the patient compliance is to improve the ingest ability of the medicine. Recently, selection of the pharmaceutical dosage forms and improvement of the ingest ability of medicines have begun to be taken into consideration during the design and development of solid medicinal forms for oral intake, from the viewpoint of improvement of the patients treatment compliance. Masking of the bitter taste of drugs is very important from the point of marketing view as well as improvement of the treatment compliance by the patients. Powder form is one of the useful dosing forms of medicines for patients who cannot swallow tablets. Ibuprofen [(RS)-2-(4-isobutylphenyl) propanoic acid], a nonsteroidal anti-inflammatory drug, is widely used in the treatment of moderate pain and fever, because of its high efficacy and safety. However, it is necessary to mask the bitter taste since it has a strong bitter taste. Although several masking methods are available to mask the bitter taste for different formulations of ibuprofen, such as adjustment of pH for suspensions, compression into chewable tablets with polymer coating of the granules for taste-masking, and addition of flavors and sweeteners, few methods have been reported to mask the bitter taste of ibuprofen in the powder form. Physical masking methods are widely applied to mask the bitter taste of drugs. The film coating method, which is one of the physical masking methods, is considered to be suitable for masking bitter taste, because of its ability to control the dissolution rate of drugs in the mouth. Several equipments with various features have been used for the film coating, especially a spouted bed with draft tube for masking bitter taste of drugs. The spouted bed with draft tube has an advantage of good coating efficiency without causing agglomerations, because the jet of air prevents cohesion of the particles. However, it also has the disadvantage of breaking weak particles because of the vigorous jet of air. Therefore, it is necessary to prepare core particles that are not broken when they are subjected to the coating process by the spouted bed with draft tube. To manufacture drug containing core particles by fluidized bed granulation, lactose granules or sugar beads are used and they are layered with drugs. However, it requires long operation time to manufacture the core particles with containing high content of drug and those particles become large. When the size grows, it becomes uncomfortable for patients to ingest powder form medicine. In this background, agitation fluidized bed granulation has gathered a special interest as a suitable manufacturing method of core particles with a high content of drugs. In the manufacture of core particles, attention must be paid to several physical properties of particles for coating process, such as adequate mass median diameter, narrow size distribution, large apparent density, spherical shape, and low friability to allow the particles to endure the coating process. Since agitation fluidized bed granulation can impart compression and shear forces to particles, it is possible to produce core particles containing high content of drug with suitable physical properties for the coating process. In order to determine the optimal operating conditions and the optimal formulation of the core particles, the effects of the various operating conditions and several kinds of excipients with varying water solubility levels were investigated. As mentioned above, care must be taken to prevent breakage of the core particles during the coating process. It is thus important to evaluate the strength of the core particles. So far, several methods have been used to evaluate the strength of the core particles, such as the rotation test and the compression test, however these methods are complicated and time-consuming, and it would appear that there are few simple-and-easy-to-use test methods that can be used to evaluate and predict the friability of core particles during the coating process. In this paper, the optimal operating conditions of the agitation fluidized bed granulation method and optimal formulation for the preparation of core particles that can be successGranulation 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