Koji Ukai

Practical approach to prepare solid dispersion drug product using spherical silicate.

The purpose of this study is to establish a novel approach for preparing a solid dispersion drug product using spherical silicate by a Wurster-type fluidized bed granulator. The spherical silicate used in this study has porous structure and ideal particle size for loading by a Wurster-type fluidized bed granulator. As model drugs, ibuprofen (IBU), indomethacin (IMC), and phenytoin (PNT) were used and the proposed approach was applied to prepare amorphous drug. All drugs could be loaded on the spherical silicate in an amorphous state. On the other hand, spray drying of spherical silicate suspended in IBU solution was conducted to prepare amorphous product of IBU as a reference; however, complete amorphization was not achieved. Dissolution profiles of each drug after loading on spherical silicate by a Wurster-type fluidized bed granulator were evaluated, and dramatic improvement of dissolution was observed compared with those of crystalline drug. In the proposed approach, specific surface area and particle size of spherical silicate were determined as a key factors to contribute to high yield of amorphous product.

Application of spherical silicate to prepare solid dispersion dosage forms with aqueous polymers.

The objective of this study is to prepare and characterize solid dispersions of nifedipine (NP) using porous spherical silicate micro beads (MB) that were approximately 100 μm in diameter with vinylpyrrolidone/vinyl acetate copolymer (PVP/VA) and a Wurster-type fluidized bed granulator. Compared with previously reported solid dispersion using only MB, the supersaturation of NP dissolved from the proposed system of MB and PVP/VA was maintained during dissolution tests. The proposed system produced a solid dispersion product coated on MB, and morphology was maintained after the coating process to prepare solid dispersion; therefore, the powder characteristics, such as flowability of the proposed solid dispersion product, was tremendously preferable to that of the conventional spray-dried solid dispersions of NP with PVP/VA, expecting to make the consequent manufacturing processes easy for development. Another advantage in the terms of manufacturing is its simple process to prepare solid dispersion by spraying the drug and polymer that were dissolved in an organic solvent onto a MB in a Wurster-type fluidized bed granulator, thus, simplifying the optimization and scale-up with ease.