Size Flashcards
What is size reduction also known as?
Comminution, pulverization, grinding or millin
reducing a solid into a smaller state of sub-division
Why do we do size reduction?
- Increase SA for reaction
- Improve extraction of active principles
- Improve dispersibility in solution
- Allow better mixing or blending**
- Enable rapid dissolution**
- Preliminary process in preparation of products**
**impt for solid dosage forms
Dec size, Inc SA, Inc Dissolubility
What is the % of energy input that affects size reduction?
And how is energy lost?
1-2% energy input affects size reduction
Energy loss by:
- elastic deformation, plastic deformation without fracture, deformation to initial cracks, deformation of machine parts
- Inter-particle friction, particle-wall friction
- heat, sound, vibration
What are the modes of milling process?
Mode I: Crack opening by tensile spreading at crack tip (Tension on both sides)
Mode II: Crack sliding by shear deformation parallel to crack direction (Shearing, opposite directions)
Mode III: Crack tearing by shear deformation perpendicular to crack direction (tearing)
What is milling?
Particles fracture (equal size parts) or abrade (chipping off small particles from a larger particle) to give smaller particles
What is the Hooke’s Law?
F = kX
F - force needed to extend or compress a spring by some amt
According to the Hooke’s Law, what point gives a successful milling process?
The supplied energy must be capable of exerting stress beyond the material’s break or fracture point.
AB - elastic deformation (reversible)
BC - plastic deformation (irreversible)
DE - Path of plastic recovery
What is the particle size distribution in milling?
Size distribution typically starts unimodal; With attrition, changes to bimodal
uni –> bimodal –> back to unimodal but in a smaller size range
What are some (3) considerations in size reduction?
- Properties of material:
- Thermolability (if not heat stable, problem)
- m.p.,
- flammability,
- deformation characteristics (deformed into hard and may not break down) - Fracture mechanisms of particles: hardness and tensile strength
- Mechanical: type of equipment
- Impact, shear or pressure
- Material in contact with product (stainless steel, SS304, 316)
- temp control (machine requires to remove excessive heat)
What are the 4 basic mechanisms for size reduction equipment causing breakage?
- Impact: particle concussion by a single force (hammer) (often used)
- Compression: particle disintegration by 2 rigid forces (nut-cracker)
- Shear: produced by particle to particle interactions (scissors) (more effective for fibrous materials)
- Attrition: arising from particles scraping against one another or against a rigid surface (grinding stone)
What are the advantages and disadvantages of wet grinding?
Size reduction in liquid media (water)
+:
- eliminate dust
- easier to handle material
- use less energy
- inc mill capacity
-:
~ inc wear of grinding medium –> some materials from machine parts enter the products
~ Not applicable to soluble materials
~ may need to dry products afterwards (Additional step)
When is roll mill best for?
Best for soft materials, e.g. cream
grind pastes; coarse crushing (like pestle and mortar)
Peripheral velocity of rolls and clearance btw rolls can be varied
What are the different ways to use hammer mill?
- popular but less precise milling
- Rotor type/ Rasping Screen: Low energy calibrating mill
- Knife-edge rotor: comminutor/ chopping mill (for herbal materials, breaks down cellulose material better)
- Impact edge: pulverisation powder grinding
blade rotor: knife and blunt edge
bar rotor: gentle action, de-lumping
What are the advantages and disadvantages of Hammer Mill Technology?
+ several models and designs
+ medium-high shear applications
+ blades and screens interchangeable
+ suitable for very hard materials; cheap and efficient too
- noisy & dusty
- can’t plug feed
- belt slippage common due to load
- high vol air generate, ventilation required
- screen selection and installation complex, not scalable
- sifting required after milling
- temp rise due to friction
What are the operating principles (steps) of cone mill?
- Infeed falls into the conical screen chamber
- rotating impeller imparts a vortex flow pattern to the infeed material
- Centrifugal acceleration forces particulates to the screen surface
- Hence, particles are continuously delivered to the “action zone” between the screen and impeller
- Here, the particles are size reduced and instantly discharge through the screen openings
What are the principles of micronising mills - vibratory ball mill?
- Tumbling balls rotate and break down particles
- Widely used for fine grinding (e.g. in pigment industry)
- extremely efficient with vibration, best wet
- balls: stainless steel, stoneware (ceramic)
- ball size and density are impt factors
- cascading or vibratory (vibro-energy)
~ cascading: long process time
~ vibratory: efficient but associated with rapid temp rise (short process times or jacketed to removed heat)
What are the principles of air jet mill (with classifer wheel)? (check slide for images)
- Uses high pressure
- Material into grinding chamber; high pressure nozzles will arrange such that all will direct the air into once particular spot
- Particles will be accelerated by air nozzle to accelerate to the middle point
- Particles will knock each other when it comes into contact
Useful for hard materials
E.g. diamond shavings into powder for polishing wheels
- If particles approach classifier wheel and particles are small, may follow the air
- Larger particles –> centrifugal force from the wheel will push it back down to break it down further
What are the principles of fluid energy mill - centrifugal separator? (check slide for images)
Air only can escape at inner
Air is extracted from inside of bowl
Finer particles will go along
Bigger particles on the outside will still go round and round until become smaller
Air will be moving; air will come to nozzle; accelerate particles and cause collision of particles; particles come from inlets and feed
Why are micronising mills - fluid energy mill and air jet mill used?
- widely used for very fine grinding
- extremely efficient, to micron sizes (1-2 microns)
- separation either by centrifugal separation (fluid jet) or use of classifying wheel (air jet)
- grinding by particle-particle impacts
- capable of milling very hard materials
- needs good process control
What are the key points to take note from milling?
- improve performance and quality of powders and to assist down stream processing such as blending and tableting
- size reduction enable particles to pack more efficiently and to improve dissolubility
- range of millers, impellers, screens avaialble
- Possible to co-mill with additives like solubilisers, lubricants
What are the 2 different types of diameters?
- Perimeter diameter (e.g. use graticule)
- Projected area diameter (e.g. use image analysis)
- sphere
What is an equivalent sphere?
weight = 4/3 pi x r^3 x density
weight of square box converted to weight of a sphere
enables calculation of one unique number (2r) for the diameter of a sphere that has the same weight as the box
- the use of a 1D property of particle (a sphere) as measurement to derive one unique number –> equivalent sphere theory
with this theory, possible to gauge if particles become bigger/smaller, according to changes in vol/wt properties,
What are the different types of sizing methods?
Major
- scales (vernier, micrometer): large particles >05mm
- sieves (popular): >10um
- microscopy/image analysis: 5um-5mm
- Laser diffraction: 5um-5mm
- Laser scattering: 0.001um-5um
Others:
sedimentation: gravity, sedimentation - 0.05um - 150um
SEM/image analysis: nm-um
AFM/image analysis: nm-um
What are the principles of microscopy?
microscopy/image analysis: 5um-5mm
- direct visual examination, cheap
- operator dependent
- few particles examined (non-representation risk)
- Must have a minimum of 10000 images (not particles) examined for statistical validity
Laborious, slow, fewer particles examined for this manual method
What types of diameter we can identify in microscopy?
- provides 2D image
- Minimum diameter ~ Feret’s diameter: dist btw 2 vertical lines tangent to ends of particle OR greatest dist possible btw any 2 points along the boundary of a region of interest
- Martin diameter: length of horizontal line that appears to divide particle into 2 halves
(Maximum particle length as the diameter = would mean, particle is a sphere)
What are the principles of sieves?
- Low-resolution method; only 4-8 fractions (layers) are provided
- good for quality control
- the longer measurement times, the smaller the sizes, as particles orient themselves to fall through the sieve
Sieves are good for coarser particle
What are the principles for Air Jet Sieve?
- sieve fine powders <200um (10-200um)
- can be used with microsieves
1. weighted material placed on sieve of certain aperture size
2. Particles smaller than aperture size passed through a sieve
3. Material remaining on sieve weighed
4. Process repeats with sieves of another aperture size
5. Cumulative graph of % wt oversize plotted
What is a span in the size distribution plot?
Mass median diameter D50 = Point A (sieve equivalent diameter at the 50% mark on the graph)
Span = (D90-D10)/D50 = (C-B)/A
Span: spread of the particles
Characterise the powder qly using the mean/median and get the span
Span is the spread of distribution
What are the principles of electrozone sensing?
- for sizing blood cells
- disperse particles in an electrolyte as a suspension
- require calibration standards that are expensive and can change size in distilled water and electrolyte
- Large particles sediment fast and not easy to size particles <2um
- Porous particles (electrolytes can enter space) and dense (settle down too quick) materials pose additional problems
- based on orifice obscuration
- size ~ area ~ resistance
- unaffected by optical properties, densities, colours and shapes of particles
- *- particles need to be insoluble, non-porous, non-conductive**
- needs reference size calibrator
Blood cells block the electrical conductivity, and thus sized accurately
What are the principles of Laser diffraction?
- low angle light scattering (LALLS)
- measure dry powder, spray / particles in air / liquid
- non-destructive, non-intrusive
- rapid, repeatable and high resolution
- no need to calibrate against a standard
How does laser diffraction works?
High angle scatter (smaller particles) and low angle scatter (larger particles)
Particles’ surface will scatter the light
Curvature of particle causes light to scatter
Big particle will scatter less (curvature more gentle, larger particles in central area), small scatter more (sharp and acute angles)
What are the principles of light scattering?
- random movement due to Brownian motion (2-3um diameter and smaller)
Pace of movement is inversely proportional to size
- smaller particles, faster movement/diffusion
Pace can be detected by analysing the time dependency of light intensity fluctuations scattered from particles when they are illuminated
How does photon correlation spectroscopy works?
Monitor scattered light
Detected by diodes
Scattered light decay overtime (the down slope)
Particles 1-5microns and below
Kinetic energy move faster
If light decay disappear very fast - small particle
If decay slowly - larger particle
Speed appear and disappear can estimate the size of particles
Statistically they can determine the size
What is the difference btw light scattering and laser diffraction?
light scattering (less than a few microns, not for large particle, depend on reflection of light. Depend on Brownian motion
and laser diffraction (Depends on diffraction principle, light passes surface, curvature, small particles are more curve, larger particles are more flattish - light passing through peak angle for small one, smaller angle for larger particles; determine how many particle diffract at larger / smaller angle)
