Particle Size Measurement Fundamentals

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Questions and Answers

What is the initial method for starting particle size measurement?

X-ray diffraction

Dynamic light scattering

Electron microscopy

Optical light microscopy (correct)

Which factor does NOT influence the accuracy of particle size measurement?

Color of the particles (correct)

Size distribution to be measured

Quantity of powder available

Formulation type

What must be considered regarding materials with a low occupational exposure limit (OEL)?

They require a smaller sample size.

They have no impact on particle size techniques.

They need to be kept at room temperature.

They must be adequately contained during measurement. (correct)

Which of the following is a mechanism involved in the liquid dispersion of particles?

Surface tension reduction Signup and view all the answers

What is often measured by techniques that do not directly measure particle size?

Particle volume Signup and view all the answers

In a sampling scheme, what is crucial to avoid bias in particle selection?

Randomization of samples Signup and view all the answers

What property of powder may affect its particle behavior before size measurement?

Water solubility Signup and view all the answers

What is a primary characteristic to consider when preparing a particle size measurement?

The physical properties of the powder Signup and view all the answers

What is the primary reason for assessing particle size during formulation?

To select appropriate excipients and ensure uniformity Signup and view all the answers

How does particle size affect the flow properties of powders?

Flow rate is inversely proportional to particle size Signup and view all the answers

What type of particles is preferable for lung delivery applications?

Very fine particles to reach deep lung areas Signup and view all the answers

Which statement best describes the impact of particle size on drug release?

Particle size influences the available surface area affecting release rates Signup and view all the answers

Which method is used for particle size analysis in the content provided?

Laser light diffraction after dispersion in butan-1-ol Signup and view all the answers

Why is it critical to control particle size during manufacturing?

To influence processing operations and product performance Signup and view all the answers

What is the magnification level of the photomicrograph of salbutamol sulphate micronised powder?

x 5560 Signup and view all the answers

What effect do fine particles have when used in suspensions?

Reduce the likelihood of a 'scratchy' feeling on the skin Signup and view all the answers

What is meant by an equivalent sphere in particle measurement?

A sphere that matches the particle in the property being measured Signup and view all the answers

What is Feret's diameter used to measure?

The distance between two tangents on opposite sides of the particle Signup and view all the answers

Which particle size method requires one dimension for regular geometric figures?

Methods for spheres, cubes, and regular tetrahedrons Signup and view all the answers

What does the equivalent volume diameter represent?

Diameter of a sphere with a volume equal to that of the particle Signup and view all the answers

Which term describes characteristics of particle shape according to the British Pharmacopoeia?

Descriptive terms Signup and view all the answers

How are particle size and shape characterized for non-spherical particles?

Through multiple dimensions and identification of shape Signup and view all the answers

What is the primary characteristic of powder particles discussed?

Their shape as a fundamental property Signup and view all the answers

What is the main effect of particle size on the combustion of black powder?

Fine grained powder burns faster than larger particles. Signup and view all the answers

Why was black powder made with larger particles historically?

To slow down the rate of burn and prevent explosions. Signup and view all the answers

What characteristic of fine powdered black powder made it more powerful?

It had a larger surface area for combustion. Signup and view all the answers

What was a disadvantage of using fine grained black powder?

It built up too much pressure too quickly. Signup and view all the answers

How does the combustion of black powder mainly occur?

On the surfaces of the particles. Signup and view all the answers

Which particle shape is characterized by the property of sphericity?

Round Signup and view all the answers

Which method does NOT contribute to the quantitative characterization of particle shape?

Qualitative description of shape Signup and view all the answers

What is the principle behind the Coulter counter in particle size measurement?

It detects changes in electrical conductivity as particles pass through an orifice. Signup and view all the answers

Which of the following is a limitation of the Coulter counter method?

Particles can clump together and give inaccurate readings. Signup and view all the answers

When studying powder packing, which particle characteristic should be primarily assessed?

General geometric shape Signup and view all the answers

What is the primary advantage of using laser light scattering for particle size analysis?

It provides high speed and high reproducibility. Signup and view all the answers

Which particle shape characterization is typically assessed using projected area ratio?

Angular Signup and view all the answers

What is a significant challenge in sieve analysis for particle size measurement?

It can be influenced by the moisture content of the particles. Signup and view all the answers

In laser light scattering, what is the relationship between scattered light angle and particle size?

Larger particles scatter light at a smaller angle. Signup and view all the answers

What assumption is made about the particles when calculating scattering in laser light scattering?

Particles are spherical and opaque to light. Signup and view all the answers

What type of distribution is typically observed in the number of fine particles compared to coarser particles?

Positive skew. Signup and view all the answers

In particle size distribution analysis, what does a 50% cumulative undersize represent?

The median size of the particles. Signup and view all the answers

When considering a particle size distribution plot, what do the values representing the lower and upper quartile indicate?

25% and 75% of the total number of particles. Signup and view all the answers

Which parameter is NOT used in the optical microscopy example for determining particle size?

Cumulative undersize distribution. Signup and view all the answers

What is suggested by a positive skew in the particle size distribution?

The distribution is centered around smaller particle sizes. Signup and view all the answers

What is the purpose of using a data processing unit in the context of laser light scattering?

To analyze and interpret the scattering data. Signup and view all the answers

Study Notes

MPharm Programme - Particle Size & Shape

This presentation covers preformulation aspects of particle size and shape.
Particle size significantly affects the burning characteristics of black powder. Fine powder burns faster and is more powerful, but creates higher pressure leading to gun explosion risks.
To solve this, larger particles with consistent size give a more controlled burn rate.
Microscopes are used to visualize a-lactose monohydrate, with magnification to show shape.
A sieve analysis was conducted on a-lactose monohydrate using laser light diffraction after dispersing in butan-1-ol. This showed the particle size distribution.
Particle size analysis is crucial for various reasons:
- Excipient selection for powder mixtures.
- Flow properties Uniformity of low-dose drugs in mixtures.
- Avoiding skin irritation and rapid settling in suspensions.
- Lung delivery of drugs. Effectiveness is reliant on particles reaching deep lung areas and having substantial surface area for absorption.
Particle size is a critical material attribute for dosage forms because it affects processing operations, performance, and thus, product quality
Several considerations must be made before measurement:
- Visual techniques (optical light microscopy).
- Data usage in relation to particle behavior (statistics).
- Formulation and presentation media.
- Particle shape and associated distribution.
- Amount of available material for sampling needs.
- Safety concerns using materials with low occupational exposure limits (OEL).

Measurement Techniques

Liquid dispersion is often applied. Dilution may not affect distribution if the dispersing fluid mimics the host fluid. Water-soluble materials can be dispersed in oil.
Mechanisms of liquid dispersion are based on surface tension reduction, ionic species changes (pH), and shear stress (e.g., ultrasound).
Particle size is often determined using methods that do not directly measure size. These methods measure something related to size and use correlation with size.
Important to understand what the method actually measures, the correlation, and how results from different techniques can be compared
Techniques include microscopy, laser diffraction, sieve analysis, light scattering, sedimentation, electrical zone sensing, ultrasound, cascade impaction, and hydrodynamic chromatography (HDC). Each technique has specific properties it measures, and associated data. The associated derived data is included in the slides.
Equivalent spheres are a useful concept. Equivalent spheres have the same physical parameter as the actual particle. Physical parameters include weight, volume, length, and least and maximum lengths. The equivalent sphere concept is useful because real particles are often not spheres.

Particle Shape

Particle shape is a fundamental property of powders and is often described qualitatively (e.g., acicular, angular, round, fibrous, flaky) using the British Pharmacopoeia.
Quantitative analysis is achieved via microscopy, with two and three-dimensional shape factors determining sphericity. The chosen method should relate to the powder-handling process, e.g., sphericity when making spherical pellets, or general geometric shape when considering powder packing.
Qualitative descriptions, like acicular, fibrous or flaky, aid characterisation.
Quantitative estimations are made from length measurements through aspect ratio, elongation, and McCarthy elongation.
Shape factors, like the Heywood shape factor (Projected Area Ratio), and circularity shape factor aid in particle shape analysis.
Methods for determining particle shape include Image analysis and conductivity.

Measurement of Particle Size

Image analysis: microscopy is used to visualize a particle. Microscopic images are converted to electrical signals so computers can analyze them for size measurements.
Conductivity: A conductivity measurement most frequently uses a Coulter Counter. A material is dispersed to an electrolyte. The number of voltage pulses are measured. This is used and related to the particle's volume from the orifice it passes through
Sieve Analysis: The sieve method uses to measure particles' properties by passing them through sieves of known aperture sizes. The weight of particles that did not pass (or did) are recorded. Sieve sizes are often between 32 – 350 micrometers. The data is related to passing through the sieve with an equivalent diameter as the sieve orifice.
Laser light scattering: The method uses a high-speed laser to measure the speed at which a material scatters light. This is used to predict equivalent volume diameter.

Particle Size Distribution

The number of fine particles typically is greater than coarser particles leading to positive skew.
Positive skew in particle size distributions is when there's a greater number of fine particles and fewer large particles. When measuring size and shape, one needs to consider that particles are not always one single shape. The use of equivalent diameter is a way to try to improve on this limitation.
Frequency analysis on plots in log-probability paper gives a visual representation of size distributions. It allows one to detect the percentages from the plot, as well as determining median sizes.
The number versus weight distribution plots show the relationships between number of particles and relative weights of that size.

Examples

Examples using microscopy, equivalent area diameter, eyepiece graticule, and plots of percent cumulative undersize distribution are included in some slides. Different materials like lactose monohydrate can be analysed using different methods.

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Description

Explore the essential concepts and techniques related to particle size measurement in this quiz. Learn about factors influencing accuracy, mechanisms of dispersion, and the significance of particle size in formulation. Test your understanding of key terminologies and methods used in this critical field.