title: Application of fluidized hot-melt granulation (FHMG) for the preparation of granules for tableting; properties of granules and tablets prepared by FHMG.
abstract: The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/ magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.
authors.affiliation: Shizuoka Pharmaceutical Research Center, Pharmaceutical Technology Research Laboratories, Daiichi Pharmaceutical Co Ltd, Haibara-gun, Shizuoka, Japan. kidokknl@daiichipharm.co.jp
authors.forename: Motonori
authors.initials: M
authors.lastname: Kidokoro
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Haramiishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Sagasaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D016062:Porosity; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D014783:Viscosity
chemical_list: D005079:Excipients; D013607:Tablets