title: Preparation of Fine Particles with Improved Solubility Using a Complex Fluidized-Bed Granulator Equipped with a Particle-Sizing Mechanism.
abstract: 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.
authors.affiliation: Research and Development Division, Sawai Pharmaceutical Co., Ltd.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Hosaka
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Okamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tokunaga
mesh_terms: D015281:Cefmenoxime / Q000031:analogs & derivatives* / Q000737:chemistry; D004339:Drug Compounding / Q000295:instrumentation*; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties
chemical_list: C046817:cefteram pivoxil; D015281:Cefmenoxime