Shouichi Hosaka

PREPARATION AND SCALE-UP STUDY OF TREATED FAMOTIDINE FOR THE DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS USING A COMPLEX FLUIDIZED-BED GRANULATOR EQUIPPED WITH A PARTICLE-SIZING MECHANISM

Objective: Bitter taste-masked drug substance should be needed for the development of orally disintegrating tablets (ODT). We selected a new type of a complex fluidized-bed granulator equipped with a particle-sizing mechanism for treating famotidine (FAM). This study was conducted to demonstrate the critical process parameter, which controls particle size of treated FAM, to determine its acceptable particle size considering uniformity of assay and to perform scale-up study from a laboratory scale to a commercial scale. Methods: Particle size of treated FAM was evaluated by changing spraying air pressure on the operation of a complex fluidized-bed granulator. Uniformity of assay in granules after blending and tablets were compared at different particle size of treated FAM. On the scale-up study, particle size and assay of treated FAM in both scales were evaluated. Results: The particle size of treated FAM decreased as the increase in spraying air pressure in relation to the spraying mist size. Better uniformity of assay was observed when the diameter of treated FAM was 20 µm compared to that of 50 µm. Therefore, target particle size of treated FAM was set at approximately 20 µm. Similar qualities could be obtained between both scales in the points of particle size and assay. Conclusion: On the operation of a complex fluidized-bed granulator, spraying air pressure was the critical process parameter that controlled particle size of treated FAM. On Scale-up study of treated FAM, spraying air pressure in relation to the spraying mist size was important.

Differences in Powder Properties of Two 1,4-Dihydropyridine-Type Compounds Evaluated through Thermal Analysis

The powder properties of two 1,4-dihydropyridine type compounds, manidipine dihydrochloride (Man) and benidipine hydrochloride (Ben), which possess similar physicochemical properties, were compared through thermal and mechanical analyses. Man and Ben were compressed with lactose monohydrate (Lac) and magnesium stearate (Mgst) at different compression forces. As an index, we focused on the onset temperatures of Lac dehydration during thermal analysis and plotted them against compression forces to evaluate the differences in powder properties between Man and Ben. To discuss in detail, the Lac ratio was selected as a formulation factor and compression speed as a process factor, which would be influenced to the onset temperature or its profile. It could be represented that Man was more adherent than Ben through thermal analysis by changing these critical factors, which were consistent with the results obtained through mechanical analysis.

Preparation of Fine Particles with Improved Solubility Using a Complex Fluidized-Bed Granulator Equipped with a Particle-Sizing Mechanism

A new type of fluidized-bed granulator equipped with a particle-sizing mechanism was used for the preparation of fine particles that improved the solubility of a poorly water-soluble drug substance. Cefteram pivoxyl (CEF) was selected as a model drug substance, and its solution with a hydrophilic polymer, hydroxypropyl cellulose (HPC-L), was sprayed on granulation grade lactose monohydrate (Lac). Three types of treated particles were prepared under different conditions focused on the spraying air pressure and the amount of HPC-L. When the amount of HPC-L was changed, the size of the obtained particles was similar. However, particle size distribution was dependent on the amount of HPC-L. Its distribution became more homogenous with greater amounts of HPC-L, but the particle size distribution obtained by decreasing the spraying air pressure was not acceptable. By processing CEF with HPC-L using a complex fluidized-bed granulator equipped with a particle-sizing mechanism, the dissolution ratio was elevated by approximately 40% compared to that of unprocessed CEF. Moreover, in the dissolution profile of treated CEF, the initial burst was suppressed, and nearly zero order release was observed up to approximately 60% in the dissolution profile. This technique may represent a method with which to design fine particles of approximately 100 µm in size with a narrow distribution, which can improve the solubility of a drug substance with low solubility.