Powders Flashcards
What is a powder
A collection of particles usually 10-100um in diameter
Bulk powder acts as a fluid
Flow isnt completely free
Manufacturing of tablets and capsules will rely on….
Flow properties of the drug and excipients
What are flow properties determined by
Particle size, shape and particle-particle interactions
A drug must ….
dissolve in GIT prior to absorption
Drug dissolution equation
Noyes-Whitney
dm/dt = DA(Cs-c) / h
dm/dt is dissolution rate
D is diffusion coefficient
A is the available surface area
cs is the solubility
c is the concentration
h is the diffusion layer thickness
Wh at is a particle
Is a single solid entity of a material usually in um size rnage
Nature of powders
Crystalline but doesnt mean single crystals
Crystal habit
External shape of Crystal - usually refers to single crystals
Monocrystaline systems
Have well defined habits - cubic, plates, needles
Polycrystalline systems
In practise most systems are poly
Composed of aggregates of micro crystals usually less than 1um
If we looked a a powder particle under a microscope
Non-uniform
Porly defines
Crystalline but composed of many tiny crystals bonded together
Complications
Individual particles can clump together to form aggregates
What does particle size mean
Hard to define
Particles can assume any shape
Each method of size analysis makes assumptions
What does it mean if a particle is monosized or mono disperse
Every particle is same size and hence population may be defined by a singular parameter
In practise we need to….
define both some sort of average size
and also the distribution around that average
Simplest way of displaying size data
Histogram where proportion is plotted against size
Histogram distributions
Symmetrical is normal distribution has one peak int he middle
+skewed and - skewed has a peak and tail on either side
Bimodal has 2 peaks
How to put numbers into distribution charts
Use the mode
Mode, median and interquartile range
Mode = size at which greatest frequency of particles occurs
Median = size at which 50% of particles are larger or smaller
IQ range = rnage between 25% and 75%
What is sieve analysis
- Set of sieves with widest mesh at top, finest at the bottom
- Sieves usually automatically shaken for a predetermined
period of time (usually around 20 minutes) - quick
- accurate
- not used often
Microscopy to measure size
- Light microscope can measure particles down to about 10 um, scanning electron microscope down to about 100 nm
- Old fashioned method
- This is a 2-dimensional technique
- size and shape
Electrical stream sensing one method
- Works on the basis of particles suspended in an electrolyte solution
- Particles pass through an aperture of known diameter. Electrodes either side of aperture will register increase in resistance as particle displaces its own volume of
electrolyte - measure volume diameter (diameter of sphere with the same volume as particle)
- used for range of 0.1-1000um
- quick and easy
- can cause blockages often
Laser light scattering methods
- Use diffraction of light as means of calculating diameter and size range
- Laser applied to suspension of particles in aqueous or non- aqueous medium
Two types: - large-particle analysers (measure 1-1000 um)
- photon correlation spectroscopy (for smaller particles, 10 nm – 1 um)
- rapid and reliable
Why is powder flow important
• Uniform feed into tableting or capsule filling equipment, leading to uniform weight and mechanical properties
• Ease of handling and transfer of powders
Adhesion and cohesion
- Adhesion – attraction between a material and a different material
- Cohesion – attraction between a material and an identical material
- Cohesive powders do not flow well
What is van der walls and wat is it dependant on
Non specific
Dependant on area of contact between particles - finer particles are more cohesive
Flow of large, small, needle and round particles
Large flow better than small
Round flow better than needles
Measurements of powder flow properties
- Angle of repose
- Bulk density measurements
- Angle o repose
Simple method of pouring powder onto a plate
Angle to horizontal measured
Powders will flow until the angle of inclination becomes too malleable to overcome cohesive forces
> 50degrees = poor flow
25degrees = good flow
- Bulk density measurements
Density of powder bed may be used to assess flow
Measure bed flow before and after consolidation by tapping it
Flow ability measured by hausner ratio Df/Do
1.2 = good flow
>1.6 = poor flow
When tap the particles get closer together
What is flow through hopper
Particle flow through orifice and over time a depression forms in upper surface. Powder falls though the central channel until an empty or dead zone forms. Particles in middle zones flow faster over the outer slower zones
What is rat holing and why worry
Problematic as there is danger of it collapsing and leading to sudden flooding. It’s where the particles build up on the sides of the hopper with a channel in the middle
Tablet and capsule manufacture are highly dependent on flow form hopper
Poor flow means non-reproducible fill and non reproducible dose
Why s powder mix important
Need even mix especially when preaparing high potency drugs
Segregated mix is a half and half. Ideal mixing is even I and then random mix
What is random mix
Probability of finding a type of particle is proportional to total number in mix
How to access randomness of mix
Take several samples and measure how many purple squares in each
3 mechanisms of mix
Convective - take a portion of material from a pile, move it to another location
Shear - powder heap will collapse into hole created (shear plane generated)
Diffusion - if powder bed lifted and dropped. Particles then tumble over each other and mix on particulate basis
Tumbling mixer
Y-cone blender
Shear and diffusive via a tumbling motion
Roller mixer
Bottle containing material placed on rotating cylinders
Gentle
Agitator mixer
Rely on motion of a blade or paddle - like kenwood
Connective and shear
Danger of dead zones if paddle doesn’t involve movement in all part of the mix
What is large and small particles mix
Smaller will absorb onto the surface of large particles
Important for aerosols
Optimal mixing time
Too long and the system seperate
Variation in particle size
Size, shape, density
Particle will behave differently
Similar particles tend to congregate
percolation segregation
Small will fall through voids
trajectory segregation
Large will have more momentum and move further distances than small
Particle shape effects
Spherical particles segregate more readily than non-spherical due to shape and SA:volume
Particles may also change shape during processing so tendency to segregate may also change
Mixing times
For non-segregated mice the longer the mixin Time the better
For segregating mixes, there is an optimum time after which the rate of segregation exceeds the rate of mixin
