難溶性薬物イトラコナゾールの固体分散体による溶出性改善

抄録

The present study investigated methods of improving the dissolution of Itraconazole, which is a poorly water-soluble and weakly basic drug (pKa of 3.7) by solid dispersion techniques using an enteric polymer, hypromellose phthalate (HP-55^®). Solid dispersions were prepared by the hot extrusion method, spray drying method and fluidized bed coating method. In the case of the hot extrusion method, it could change the drug phase from a crystal to an amorphous state in order to prepare the solid dispersion at a 17:10 drug to HP-55 ratio. However, the dissolution rate of that solid dispersion in JP XV 1st fluid could not be improved because of the enteric property of HP-55. Solid dispersions containing the drug in an amorphous state could be prepared using the spray drying method and fluidized bed coating method with a lower concentration of HP-55 than the hot extrusion method. It was found that these solid dispersions showed a relatively improved to dissolution rate (more than 70%) in JP XV 1st fluid as a result of the decrease in HP-55 content. Further, it was found that the dissolution rate could be improved to more than 80%, when the mean diameter of solid dispersion particles prepared by the fluidized bed coating method was controlled to less than 120 μm. This study demonstrated that dissolution of Itraconazole in JP XV 1st fluid could be improved by selecting the fluidized bed coating method and controlling the mean diameter of solid dispersion particles, as well as using an enteric polymer as an excipient of solid dispersion.