Nano-pulverization of poorly water soluble compounds with low melting points by a rotation/revolution pulverizer

Pharmazie. 2012 Aug;67(8):681-6.

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.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anticholesteremic Agents / chemistry
  • Anticonvulsants / chemistry
  • Calorimetry, Differential Scanning
  • Crystallization
  • Drug Compounding / instrumentation*
  • Fenofibrate / chemistry
  • Flurbiprofen / chemistry
  • Hypolipidemic Agents / chemistry
  • Nanotechnology / instrumentation*
  • Particle Size
  • Pharmaceutical Preparations / chemistry*
  • Phenytoin / chemistry
  • Probucol / chemistry
  • Solubility
  • Waxes
  • X-Ray Diffraction

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticholesteremic Agents
  • Anticonvulsants
  • Hypolipidemic Agents
  • Pharmaceutical Preparations
  • Waxes
  • beeswax
  • Flurbiprofen
  • Phenytoin
  • Probucol
  • Fenofibrate