Size Reduction and Measurement

Question 1

Why is size reduction of particles important?

Answer 1

• increase surface area for reaction, thereby improving product dispersability and allowing for more rapid dissolution.
• this consequently improves blending and mixing, as well as the extraction of APIs

Question 2

What is the relationship between particle size and dissolubility?

Answer 2

Decrease in size –> increase in surface area –> increased dissolubilty

Question 3

A lot of energy is used for particle size reduction (T/F)?

Answer 3

False. Only 1-2% of energy input is used for particle size reduction.

Question 4

Describe the different modes of milling.

Answer 4

Mode I: Crack opening by tensile spreading at crack tip.
Mode II: Crack sliding by shear deformation parallel to crack direction.
Mode III: Crack tearing by shear deformation perpendicular to crack direction.

Question 5

Describe Hooke’s Law.

Answer 5

F=kX

where F is the force required to extend or compress the spring by some amount, X is strain proportional to that amount.

Question 6

Describe the particle size distribution in milling.

Answer 6

Size distribution typically starts off unimodal. WIth attrition, changes to bimodal.
Eventually back to unimodal, but in a smaller size range.

Question 7

List the methods for size reduction.

Answer 7

1. Wet grinding
2. Roll mill
3. Hammer mill
4. Cone mill
5. Micronising mill

Question 8

Describe wet grinding.

Answer 8

• size reduction in a liquid media

Question 9

Describe roll mill.

Answer 9

• used to grind pastes, coarse crushing
• equipment comprises 2 horizontal rolls that are equal in size, are arranged side by side and rotate towards each other at different speeds.
• material goes between the rolls, is milled into smaller pieces.

Question 10

Describe hammer mill.

Answer 10

• rapidly moving hammers strike particles repeatedly until they are reduced to a size that can pass through the screen.
• higher speed will result in smaller particles.
• blade selection: blade rotor has knife and blunt edges, is used to chop particles up, bar rotor has gentle action, is used to delump.
• end particle size is usually between 150-600 micrometers.
  » screen size determines particle size, therefore use a smaller screen if you want to get a smaller particle.
• advantages:
  » medium to high sheer applications
  » suitable for very hard materials

Question 11

Describe cone milling.

Answer 11

• particles fall into the conical chamber where they are vortexed by the rotating impeller.
• centrifugal acceleration will force particles to the surface of the screen where they are size reduced between the screen and the impeller.

Question 12

Describe micronizing mill.

Answer 12

• Used for fine grinding
• Balls are placed together with the particles and are ground.
• Method of ball milling: cascading (long process time) or vibratory (shorter, associated with temperature rise)
• Air jet mill and fluid energy mill: widely used for very fine grinding of hard material to micron sizes.

Question 13

Summary pointers for milling

Answer 13

• milling is used to improve performance and quality of powders, as well as to assist in down stream processing (e.g. blending and tableting).
• size reduction is required to enable particles to pack more efficiently and to improve dissolubility.
• possible to co-mill with additives such as solubilizers.

Question 14

How can one crudely determine particle size?

Answer 14

• by the equivalent sphere method.
• sphere is drawn around the particle, volume of sphere is calculated.
• method can be used to calculate changes in particle size and weight as well.

Question 15

What are methods used for particle sizing?

Answer 15

1. microscopy
2. sieving
3. electrozone sensing
4. laser diffraction
5. light scattering

Question 16

Describe microscopy.

Answer 16

• used to examine maximum particle length and minimum diameter/Feret’s diameter/Martin’s diameter.
• (+): direct visual examination, is relatively cheap.
• (-): operator dependent

Question 17

Describe sieving.

Answer 17

• air jet sieve (used to sieve powders smaller than 200 micrometers.
• weighed material is placed on sieve of certain aperture size.
• particles smaller than aperture size are passed through the sieve.
• material remaining on sieve is weighed, process is repeated with sieves of other aperture sizes.
• cumulative graph of percentage weight over size is obtained.
  » Mass median diameter: diameter at 50% of cumulative weight.
  » Span: (D90-D10)/D50

Question 18

Describe electrozone sensing.

Answer 18

• based on the concept of orifice obscuration.
• the larger the particle size, the larger the area of aperture blocked, the less cross-sectional area is available to conduct electricity, the lower the resistance.

Limitations:

• needs reference size calibrator
• calibration standards are expensive, can change size in distilled water and in electrolytes.
• large particles sediment fast
• not suitable for porous and dense materials.

Question 19

Describe laser diffraction.

Answer 19

• Measures particle size distributions by measuring the angular variation in the intensity of light scattered as a laser beam through the sample.
• small particles have sharper curvature when scattered, will result in high angle scatter.
• large particles scatter light at smaller angles.

Question 20

What are the advantages of laser diffraction?

Answer 20

• wide dynamic range
• non-destructive and non-intrusive
• rapid processing time

Question 21

Describe light scattering.

Answer 21

• based on random particle movement due to Brownian motion.
• pace of movement is inversely proportional to particle size.
• the larger the particles and the higher the concentration, the more intense the glow will be.