The science and technology of small particles is called micromeretics.
(Ansel page 167)

Particles of different size behave differently and are evaluated differently.
The table below gives some indication as to the relationship between particle
size and examples of which products might contain that size particle. The
smallest particles are found in Colloids while the largest particles of
interest to the pharmaceutical industry are those used in making tablets
and capsules.

Particle Size | Examples | ||

Micrometeres | millimeters | seive size | |

<0.5 | <.0005 | Colloids, Tobacco Smoke, Microorganisms | |

0.5 - 10 | .0005 - 0.01 | Suspensions, Emulsions, Bacteria & Red Blood Cell | |

10 to 50 | .01 to .05 | Flocculated Suspension & Pollens | |

50 to 100 | .05 to .10 | 325 to 140 | Fine powders, Flour, Mist, Thickness of a human hair |

150 to 1000 | .15 to 1 | 100 to 18 | Coarse Powder, Drizzle, Beach Sand |

1000 to 3360 | 1. to 3.36 | 18 to 6 | Granule Size |

Rarely do we have a powder that is not a collection of particles
of different sizes. It is therefore important to know both the average
particle size and shape and the distribution of the particle size range
in the powder. Too many small particles will not allow the powder to mix
well or flow through the tablet and capsule manufacturing equipment. Please
remember that when we discuss a pharmaceutical powder it is normally a
mixture of chemicals ( the active drug and excipients) not just a pure
chemical.

Edmundson has derived a general equation for the average particle size
whether it be an arithmetic, geometric, or harmonic mean diameter.

Where n is the number of particles in a size range, d is the average
diameter of the particles in that range, p is an index related to the size
of the particle, and f is a frequency index. (The pharmaceutical uses of
each of the possible values of "p" and "f" in different situations are
also included in the table below.) I have also included a second table
with an example of some data collected on a sample of powder.

p | f | Type of mean | Size Parameter | Frequency | Comments |

1 | 0 | Arithmetic | Length | Number | Useful if size range is small. |

2 | 0 | Arithmetic | Surface | Number | Average Surface Area |

3 | 0 | Arithmetic | Volume | Number | Average weight of particles |

1 | 1 | Arithmetic | Length | Length | Of no use |

1 | 2 | Arithmetic | Length | Surface | Important Pharmaceutically |

1 | 3 | Arithmetic | Length | Weight | Sometimes useful |

Size Range | Mean Size | Number of Particles | nd | nd2 | nd3 |

.5 to 1 | .75 | 2 | 1.5 | 1.13 | 0.85 |

1 to 1.5 | 1.25 | 10 | 12.5 | 15.63 | 19.54 |

1.5 to 2 | 1.75 | 22 | 38.5 | 67.38 | 117.92 |

2 to 2.5 | 2.25 | 54 | 121.5 | 273.38 | 615.11 |

2.5 to 3 | 2.75 | 17 | 46.75 | 128.56 | 353.54 |

3 to 3.5 | 3.25 | 8 | 26 | 84.5 | 274.63 |

3.5 to 4 | 3.75 | 5 | 18.75 | 70.31 | 263.66 |

Sum | 118 | 265.5 | 640.89 | 1645.25 |

Edmondson value for p = 1 and f = 2 is 2.57

There are several other methods for evaluating the powder sample based
on its particle size distribution. All have some uses but none are perfect.
As long as each subsequent sample of the powder is evaluated in the same
way we can make predictions as to its performance in the equipment and
in use.

Optical Microscope

Sieving

Sedimentation - Andreasen Apparatus - This uses a modification of stokes
law.

d = SquareRoot {[18Viscosity h]/[(rho - rho)gt]}

Density - True and Apparent - what is the difference??

Flowability - Angle of repose - How do we measure it??

Compressability - Elastic vs plastic deformation - which one is needed in tablet manufacture??