title: Nano-pulverization of poorly water soluble compounds with low melting points by a rotation/revolution pulverizer.
abstract: We report a method for pulverizing poorly water soluble compounds with low melting points to nanoparticles without producing an amorphous phase using a rotation/revolution pulverizer. Fenofibrate, flurbiprofen, and probucol were used as crystalline model compounds. They were suspended in a methylcellulose aqueous solution and pulverized with zirconia balls by the rotation/revolution pulverizer. Beeswax, an amorphous compound, was also examined to investigate whether nano-pulverization of a compound with a low melting point was possible. Beeswax was suspended in ethyl alcohol cooled with liquid nitrogen and pulverized with zirconia balls by the rotation/revolution pulverizer. By optimizing the pulverization parameters, nanoparticles (D50 < 0.15 microm) of the crystalline compounds were obtained with narrow particle size distributions at a rotation/revolution speed of 1000 rpm and a rotation/revolution ratio of 1.0 when the vessel was 0 degrees C. Amorphous fenofibrate and flurbiprofen were not detected by differential scanning calorimetry or powder X-ray diffraction, whereas small amounts of amorphous probucol were detected. Beeswax was pulverized to nanoparticles (D50 = 0.14 microm) with ethyl alcohol cooled with liquid nitrogen. Fine nanoparticles of these poorly water soluble compounds with low melting points were obtained by controlling the rotation/revolution speed and reducing the vessel temperature.
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan. yuminoki@pharm.setsunan.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Yuminoki
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Numata
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Takatsuka
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D000924:Anticholesteremic Agents / Q000737:chemistry; D000927:Anticonvulsants / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding / Q000295:instrumentation*; D011345:Fenofibrate / Q000737:chemistry; D005480:Flurbiprofen / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000737:chemistry; D036103:Nanotechnology / Q000295:instrumentation*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010672:Phenytoin / Q000737:chemistry; D011341:Probucol / Q000737:chemistry; D012995:Solubility; D014885:Waxes; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; D000927:Anticonvulsants; D000960:Hypolipidemic Agents; D004364:Pharmaceutical Preparations; D014885:Waxes; C038228:beeswax; D005480:Flurbiprofen; D010672:Phenytoin; D011341:Probucol; D011345:Fenofibrate