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Mills and Grinders - "Top-Down Particle Size Reduction"

Milling and grinding are ancient techniques that are working their way into high-tech markets. Kyle James, VP of sales at Retsch USA (Newtown, PA) notes that demand for particle size reduction systems has grown significantly from “alternati

Milling and grinding are ancient techniques that are working their way into high-tech markets.

Kyle James, VP of sales at Retsch USA (Newtown, PA) notes that demand for particle size reduction systems has grown significantly from “alternative” industries. “Demand from the energy sector has been substantial, particularly for processing biomass materials such as wood, refuse, and even garbage,” Mr. James says.

The breadth of life science applications has given rise to fierce competition between homogenization and milling/grinding. Both have utility in this area, but the tug of war between competing methods goes on.

Fatty acid sample preparation from animal or plant cells is usually conducted with a high-speed emulsifier (e.g., the Ultra-Turrax from IKA Works). The technique, according to literature from Spex Sample Prep (Metuchen, NJ), may be unsuitable for high-throughput labs. Until recently, high-throughput, mechanical cell disruption based on grinding employed traditional ball or swing mills adapted to microtiter plate formats.

The pharmaceutical industry has been hit hard by patent expirations and a dearth of new drug approvals. With chemical innovation lagging, drug developers increasingly turn to novel formulations to improve prospects for both old and new compounds. Nanotechnology— the creation of submicron-sized particles of drugs and ingredients—has played a significant role in these efforts.

Nanoformulated drugs dissolve and enter tissues more easily than large crystals, and may even be used to create oral dosage forms and injectable suspensions. Bill Henry, executive VP at Jet Pulverizer (Moorstown, NJ), notes that ball and jet mills have traditionally been used to reduce particle sizes down to just below 1 micron, normally the upper-size domain limit for all things “nanotech.” “That’s the focus for these mills, particularly for electronics and battery applications,” says Mr. Henry. In pharmaceuticals, he adds, milling may be thought of as a “pregrind,” or precursor to nanoparticlegenerating milling processes.

Yet for some pharmaceuticals, the higher end of the nano-size domain might be just what the doctor ordered. Ball milling is being investigated extensively for drug particle size reduction; the manufacturing processes for five approved drugs already use milling.

Two basic strategies exist for creating submicron-sized drug particles. The “bottom up” approach involves precipitation or chemical synthesis; the “top down” approach uses jet milling, wet ball milling, and HPH.

These methods may be combined; for example, bottom-up plus topdown (precipitation to supra-micron particles followed by milling) or topdown plus top-down (micronization followed by nanonization).

HPH, which produces the finest particles of the three techniques, employs a piston-gap homogenizer in water at room temperature. As drug suspensions pass through a “homogenization gap,” the particles are ripped apart during the collision of two fluid streams as a result of their impact with neighboring particles plus shear and cavitational forces.

Jan Möschwitzer, Ph.D., who heads early pharmaceutical development at Abbott Healthcare Products (Weesp, The Netherlands) suggests that in selecting a particle size reduction technology, drug developers first consider the bioavailability and pharmacokinetic parameters desired for a specific therapeutic. Perhaps equally important is how easily the size reduction method scales to manufacturing.

EcoMet® 250/300 Pro Grinder-Polisher

  • Stores and recalls 32 methods via touch-screen controls
  • Features adjustable power head speeds from 30 to 60 rpm (250 model), or 60 to 150 rpm (300 model), both in 10 rpm increments
  • Z-axis function removes material by depth instead of time


IM4000 Hybrid Ion Milling System

  • Capable of both cross-section and flat ion milling
  • Uses a wide Argon ion beam to irradiate specimens and uses the sputtering effect to polish the surface without stressing it
  • Features a high milling rate ion gun with a processing speed of 300 μm/hr
  • Suitable for various industries, including semiconductors, materials, research and quality control

Hitachi High Technologies America

ZM 200 Ultra Centrifugal Mill with New Cyclone

  • Features gentle and very rapid size reduction by pre- and fine grinding in one run
  • Includes patented cassette system for maximum sample recovery and easy cleaning
  • Provides a wide speed range from 6,000 to 18,000 rpm
  • Allows comfortable parameter setting via display and ergonomic 1-button operation


6970 EFM Enclosed Freezer/Mill

  • Features a totally enclosed liquid nitrogen (LN) auto-fill system with external loading of sample vials
  • Includes a pre-cooling chamber, allowing additional samples to be cooled while the grinding chamber is in operation
  • Controlled by a color touch screen interface that can store up to 10 programs for rapid process replication and consistency

SPEX SamplePrep