Lecture 9 - Particle Science I Flashcards
What can particle size effect?
drug bioavailability
settling rate (suspensions)
possibility of obtaining homogenous mixtures (and maintaining it)
flowability
other properties important for transformation into tablets and capsules
tolerability of some dosage forms
What is a way to reduce particle size?
Milling
How can we select powders of desired size?
Sieving
What are cutting methods?
the material is cut by one or more blades
Give an example of a cutting method?
cutter mill
- the starting material is fed into this and there is a rotating propellor inside with blades, which cut the material
it also has stationary blades and a screen so the cut product falls through the bottom and is collected
What are compression methods?
A pressure is applied to reduce particle size
Give an example of a compression method?
Compression mills eg roller mills
one roller is driven and the other is still, we feed our material into the top and this process begins to break down the particles
the second ball moves due to friction
What is an example of a traditional compression method?
mortar and pestle
What are impact methods?
Particles are hit by a moving surface or moving particles hit a surface
Give an example of an impact method?
Hammer mill
starting material is fed into the machine and inside there is a rotating disc with hammers attached
at the bottom there is a milling screen so particles that are small enough can fall through and are collected
What are attrition methods?
applying pressure AND friction to break down particles
Give an example of attrition methods?
roller mills
3 rollers aligned horizontally with an adjustable gap, the material is fed through the gap and the balls rotate at different speeds
the material is sheered as it is passed through the gap
material is transferred from the slower roller to the faster roller
a scraper is used to collect material
What type of force is a ball mill?
combined impact and attrition methods
How does a ball mill work?
we put our material in a drum and add balls (made of steel, ceramic etc)
the balls move around within the space to break down the material
the speed at which the drum is turned is critical
What happens if a ball mill is moved too slowly?
the balls will sit at the bottom and not come into contact with the material
What happens if a ball mill moves too quickly?
the balls will be pushed to the walls of the drum and are not breaking down the material
What is the fluid in a fluid energy mill?
Air
How does a fluid energy mill work?
there is an inlet of solid material and there is air flowing around the circuit
the inlet creates turbulence so the solid collides with the walls of the system and between themselves which reduces particle size
the material is removed and collected
How is the appropriate mill chosen?
depends upon what particle size we need to obtain
characteristics of the material
other factors e.g. cost, time, stability of the ingredients
What material are cutter mills good for?
elastic, fibrous materials like roots and wood
What materials are attrition methods good for?
Ointments, solids in suspension and pastes
What materials are impact methods good for?
brittle materials
What is the approximation made when analysing particle size?
particles are spheres (equivalent diameter)
What is the projected area diameter?
(da) we squeeze the area of the particle in a circle, this is the diameter of the corresponding circle
What is the projected perimeter diameter?
(dp) draw a perfect circle around our particle and measure the diameter
What is the size of the particle dependent on?
the orientation
What is Feret’s diameter?
(df) the mean distance between 2 parallel tangents of the projected outline of our particle
What is Martin’s diameter?
(dm) the mean short length which are the bounds of 2 separating equal particle diameters
Does martin’s diameter change with orientation?
No it is the same for the different orientations
What are direct ways to analyse particle size?
sieving the particle
microscopy - looking down the microscope to determine the size
Indirect methods to analyse particle size?
they determine a parameter correlated with size
e.g. sedimentation rate and permeability
Ideally what particle size distribution do we want?
monosized - all particles are essentially identical
what distribution of particle size do we often see?
Normal distribution - most of the particles are of one size
What is the size range of light microscopy?
1-1000um
What is light microscopy?
A drop of very diluted suspension is placed on a microscope slide and particles are measured in relation to the equivalent diameter chosen (da, dp, df, dm)
What is the size range of electron microscopy?
as low as 0.001um
What are the types of electron microscopy?
scanning electron microscopy (SEM)
transmission electron microscopy (TEM)
What is scanning electron microscopy?
this uses electrons to look at our sample and improves the resolution
gives a 3D image, gives info on shape
expensive, requires a high level of operator expertise
What is transmission electron microscopy?
we slice through our particles and look
particles are suspended in plastic and we slice them, put them on a microscope and look at them
if done properly we can see inside the particles
Size range of coulter counter?
0.1 to 1000um
What does a coulter counter measure?
the volume of particles
How does a coulter counter work?
It has a negative and positive electrode solution phase and a small gap
particles are drawn through this gap by a vacuum, as they flow through they block the gap
this changes the electrical resistance and by computing this we can tell how big the particles are
What are laser light scattering methods?
uses light to measure particle size - the laser light interacts with particles
How does laser light scattering work?
light is diffracted by particles by an angle that is inversly proportional to the volume of the particles
a detector analyses the radiation diffracted by the particles
What are the most commonly used lasers in laser light scattering?
Helium and neon lasers
What are sieves classified based on?
the sieve aperture diameter (expressed in um)
What does a sieve 1000 mean?
the sieve aperture is 1000um (i.e. 1mm)
What is the sieve aperture diameter?
the distance between two consecutive wires
How do sieve methods work?
Sieves pull out certain fractions of the material, we can stack sieves with different mesh sizes and all the material goes through, it will separate depending on size
What is sedimentation rate based on?
stoke’s equation
How does separation by sedimentation work?
we give the particles time to settle, the larger particles will travel a longer distance compared to small ones
through this process we can measure out particles sizes
What is the best way to do separation by sedimentation?
Using an andreasen pipette
can take small samples at different times
How does cyclone separation work?
particles are suspended in a fluid
air flow creates a vortex
the large particles will drop out at the bottom because the gravitational pull is stronger than the process
as the vortex changes direction at the bottom, it takes small fine particles up with it and larger ones that are too heavy will fall out
What is the fluid in cyclone separation?
Air
What is elutriation methods?
elutriation force wants to pull the particles up, but for larger particles gravitational pull is stronger
sedimentation will win for larger particles but for smaller particles, the driving vector is the elutriation so these will be taken up
What is fluid direction in relation to sedimentation direction?
OPPOSITE
