Comminution Flashcards
(24 cards)
Which is the size of particles used in aerosol products for dry powder inhalers (DPIs)?
Which is the size of particles used in aerosol products for dry powder inhalers (DPIs)?
0.5-1 µm
larger particles stay on nose compartment- sediment- too small can clear out so have to be the right size to deposit in to the lungs
Particles obtained with vibrational ball mill are:
A. Relatively small due to combined impact and attrition.
B. Relatively big due to repeated impact caused by vibrational forces.
C. Relatively small due to repeated impact and combination of vibrational forces.
D. Relatively big because only 20% of the space is filled with powder.
Relatively small due to repeated impact and combination of vibrational forces.
Combine different ways to achieve different particle size and achieve a monodispersed powder.
Which of the following method is used to accurately and precisely measure particle size?
Microscopy- only method allows you to measure the size and shape of the particles- more accurate way to measure them
Particle size of the drug (API) and other excipients (powder form) in the formulation influences what?
- Physical performances of the medicine e.g. dissolution rate
- Pharmacological effects of the drug
- Accumulation of micro-particulates after parenteral administration
NOTE: plasma proteins and their interaction with particles might increase the final size in the blood stream
Importance of particle size: delivery
Smaller particles dissolve faster, hence the bioavailability is higher
How can particle size influence manufacturing steps?
- Dose/quantity of ingredients is controlled by volumetric filling e.g. capsules
- Flow and packaging properties
•Quality control at the manufacturing end
In volumetric filling, interference with the uniformity of fill volumes can alter what?
The mass of drug incorporated into the tablet or capsule and hence adversely affect the content uniformity of the medicine
Is it easier to predict the behaviour of a powder with monodispersed particles or when using a powder with a broad and non homogenous size distribution?
monodispersed and homogenous
Ideal vs real particle shapes
spherical ideal
irregular= real
Methods for particle analysis- microscope analysis
Carried out on two-dimensional images of particles which are generally assumed to be randomly oriented in three dimensions.
In many cases, this assumption is valid.
Using a conventional light microscope, particle size analysis can be carried out using a projection screen
Particles are compared with the two sets of circles and are sized according to the circle that corresponds most closely to the equivalent particle diameter being measured.
Electron microscopy can be used when the size of particles is smaller than 100 microns.
Methods for particle analysis- mechanical sieve analysis
Sieve analysis utilizes a woven, punched or electroformed mesh, often in brass or stainless steel.
Sieves have known aperture diameters which acts as a physical barrier to particles.
Most sieve analyses use a series, stack or ‘nest’ o sieves, with the smallest mesh above a collector tray followed by meshes that become progressively coarser towards the top of the stack.
To be noted that sieving is rarely complete as some particles can take a long time to orientate themselves over the sieve apertures and pass through.
Methods for particle analysis- laser diffraction analysis
When particles are in suspension, sedimentation can be used.
With the limitations of gravitational sedimentation when particles of diameters lower that 5 μm as measured as particle settling becomes prolonged and is subject to interference from convection, diffusion and Brownian motion.
In this case, laser scattering techniques are quite useful.
In fact, for particles that are much larger than the wavelength of light, any interaction with particles causes light to be scattered in a forward direction, with the angle of scatter being inversely proportional to the particle diameter producing it.
Particle size distribution- what can be used to identify the different size ranges?
•Ideal monodispersed particle population consists of spheres (or equivalent spheres) of the same diameter
– The size of each particle can be described by a single diameter or equivalent sphere diameter
•Most powders contain particles with a range of different equivalent diameters i.e. polydispersed or heterodispersed.
Range from size distribution plots- mainly histograms
Mean particle size- why do we use this?
- A single number cannot represent (or fully describe) the size distribution of a powder
- BUT: to keep things simple, it is necessary to use one value to describe the powder sample
- Median or Mode can be used to represent the tendency of the sample/batch
- The mean diameter is more informative
Powder particle sizes
- Coarse powder >350 μm
- Medium/fine powder 100-350 μm
- Fine powder 50-100 μm
- Very fine powder 10-50 μm
- Micronised powder <10 μm
Comminution of Drugs
the process of reducing the particle size of a solid substance to a finer state of subdivision
reduction of solid materials from one mean particle size to a smaller mean particle size
When designing the comminution process, which properties of the initial powder is important to consider?
Toughness;
Hardness;
Additional Energy requirements
Particles shape
Milling
Milling is one step of manufacturing that aims to reduce the size of particles thanks to a mechanical action
Roller mills use the principle of attrition to produce size reduction of solids in suspensions, pastes or ointments.
The rollers rotate at different speeds so that the material is sheared as it passes through the gap
During the milling process, the size distribution change.
A determined milling time is necessary to guarantee the shift from mono-disperse larger particles To mono-disperse smaller particles
difficult to design a process to reduce particles to very small size range and keep an even/homogeneous particle size distribution!
Cutting methods: Cutter mill
- Fracture of particles occurs during milling between knives/blades
- Coarse degree of size reduction in dried granules due to high shear rates
Key Feature:
Series on knives/blades on a rotor.
Self-classifying method (optional):
A screen acts to retain material larger than a specified size
Compression methods: Roller mill
•The material is compressed by frictional forces as it pass between rollers
- One roll is mechanically driven, the other rotated by force transmission
- Series of rolls can be included to obtain smaller particles
Impact methods: Ball/Vibration mill
Filled up from 50% to 80% total volume with porcelain or stainless steel balls;
•The speed of rotation is an important factor
•Inclusion of vibration to conventional ball mill add impact and attrition for particle size reduction;
•Self-classifying method: a screen at the base of the mill allows particles to exit.
Separation methods
- Agitation methods (A): oscillation, mechanical vibration, gyration (most efficient)
- Brushing methods (B): a brush orientate particles and prevent blocking of the sieve surface. It is fundamental that the brush does not force particles through the sieve.
- Centrifugal methods (C): a high speed rotor generate are flow that pushes bigger particles outwards, while fine powders are processed
Size separation methods are used to obtain what?
•Size separation methods are used to obtain Quality Controlled mono-dispersed powders, e.g. known mean particle size, size range within acceptance criteria.
Size reduction methods are selected as what?
•Size reduction methods are selected as function of material, manufacturing processes and formulation requirements;
