Nanoparticulation of poorly water soluble drugs using a wet-mill process and physicochemical properties of the nanopowders.
In order to improve the dissolution and oral absorption properties of poorly water soluble drugs such as omeprazole, albendazole and danazol, various dispersing agents were added to prepare nanopowder formulations using an ULTRA APEX MILL, which is a wet-mill instrument, and their physicochemical properties were evaluated. Using Pluronic F-108 or F-68 as dispersing agents, slurries containing drug particles having nanometer size were obtained for all model drugs tested. Omeprazole, a heat labile drug, was not degraded by wet-milling and the omeprazole nanoparticles in a milled slurry did not aggregate for 24 h after wet-milling. After lyophilization of these milled slurries containing drug nanoparticles, fine solid white nanopowders were obtained. Scanning electron microscopy (SEM) suggested that the model drugs were milled into nanometer size. X-ray powder diffraction (XRPD) patterns and Differential Scanning Calorimetry (DSC) curves confirmed that all milled drug nanopowders were crystalline, although milling of albendazole nanopowder transformed it to another crystal form. Wet-milling using an ULTRA APEX MILL offers a highly effective approach to produce stable drug nanopowders and is a very useful tool for bioavailability enhancement of poorly water soluble and heat labile drugs.
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima 737-0112, Japan. y-tanaka@ps.hirokoku-u.ac.jp
Yusuke
Y
Tanaka
Mitsugi
M
Inkyo
Ryoko
R
Yumoto
Junya
J
Nagai
Mikihisa
M
Takano
Shunji
S
Nagata
D015766:Albendazole / Q000737:chemistry; D000897:Anti-Ulcer Agents / Q000737:chemistry; D000981:Antiprotozoal Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003613:Danazol / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004965:Estrogen Antagonists / Q000737:chemistry; D005612:Freeze Drying; D053758:Nanoparticles / Q000737:chemistry*; D009853:Omeprazole / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D011208:Powders / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
D000897:Anti-Ulcer Agents; D000981:Antiprotozoal Agents; D004965:Estrogen Antagonists; D004364:Pharmaceutical Preparations; D011208:Powders; D013501:Surface-Active Agents; D014867:Water; D020442:Poloxamer; D015766:Albendazole; D009853:Omeprazole; D003613:Danazol