advanced mixing Flashcards
how are fine particles classified?
fine particles may be classified as < 50 micrometeres
what size are the particles we deal with for the lungs?
1-10 micrometeres
what will influence particle size in a powder?
particle properties such as nature, size, shape & surface roughness will influence forces
what are ideal properties of particles?
- Uniform particles with mono-dispersion
- Uniform density
- Non-cohesive
- No agglomeration
- No compaction
- Excellent flowability
- Readily dispersed when delivered as an aerosol
in reality what are the properties that fine particles pose as challenges?
- Polydispersity
- Particlesize range 0.5 –10 μm
- High energy input for micronisation
- Less integral crystalline surface -amorphous regions
- Particle shape
- Particle density/porosity• Cohesive
- Hygroscopicity
- Chemical instability
- Electrostatic charge
- Poor flow properties
- Batch-batch variability
what is s used to reduce the size of the particles to micron level (1-10 mm)?
air jet mill
what is micronisation not suitable for?
not suitable for thermolabile drug and induces electrostatic charges
•Creates a large surface area to mass ratio. Therefore, powder becomes cohesive, poorly flow a bleand produces difficulty in powder device filling and aerosolization
•Particle morphology, density and composition cannot be controlled during micronisation.
how do you produce free flowing, less cohesive and more easily dispersed/aerosolized particles?
- Spray drying
- Large porous particles
- Supercritical fluids
what is spray drying?
evaporation of drug solution/suspension droplets atomized into a hot air stream.
High yield, continuous and scalable manufacturing process.
what would spray drying be suitable for?
•Ideal process for producing inhalation particles of labile macromolecules. •Suitable for processing hydrophilic (spray drying from the aqueous solution ) or hydrophobic (spray dry from the organic solvent solution) compounds
how can spray drying be manipulated?
Particle size, density, morphology and surface properties can be manipulated by controlling the process conditions or co-spray drying with excipients
what properties do large porous particles have?
The particles have a low density -large geometric size but small aerodynamic particle size distribution
•The particles exhibit superior aerosolization performance and handling due to the particle morphology
what is a supercritical fluid?
•Supercritical CO2•Crystallisation from supercritical solutions –following supersaturationinduced by varying temperature and pressure. •Or if solid insoluble in SCF (anti-solvents) –gas dissolves in organic liquid and lowers ‘solvent power’ –causes precipitation•promotes nucleation and yields very small and regularly sized particles even down to 5-2000 nm.•Pure crystalline with no defects
what Important particle properties that explain ordered mixing & DPI performance?
•bulk properties –true density , tapped density, packing fraction & porosity under different conditions
•electrostatic properties. Capacitance & resistivity (sensitive to method, degree of compaction & moisture). Literature full of contradictions –experimental results rarely reflect theory
•contact angle –if high, lower uptake, non-uniform wetting. At low RH (30 %) capillary interactions –hydrophilic and hydrophobic particles. If hydrophobic, may get stronger meniscus bridges due to poor wetting
•moisture content and uptake at selected RH. Ordered mix –parabolic relationship between adhesion strength and RH?
size & shape distribution
•surface area
•adhesion –interparticulate& contact surface
•SEMs –surface features inclevidence of dissolution
•surface roughness
how does Adhesion/autoadhesion of solid particles occur?
- mechanisms –Rumpf
- solid bridges
- chemical reaction
- melting –pressure, friction (processing)
- deposition during drying –crystallisation
- Bonding due to moisture
