What is particle size distribution?
Particle size distribution (PSD) is the means of measuring the number of particles by mass and size to calculate a size and mass range. This process can be applied to powders, granules, and particles dispersed in fluids. In theory, a particle size distribution is obtained by taking the minimum diameter and standard deviation of a perfect sphere, assuming a normal distribution.
In pharmaceuticals, the process of determining PSD is generally more complex as particles are rarely perfect spheres, do not conform to a normal distribution due to blends of different sized materials, and can contain large numbers of small particles (fines). For these reasons, it is necessary to have a particle size quantification system better suited to the specific requirements of the pharmaceutical industry, and D-values fit this requirement well.
What is d10 d50 d90 in particle size distribution?
D-values can be thought of as a mass division diameter. It is the diameter which, when all particles in a sample are arranged in order of ascending mass, divides the sample's mass into specified percentages. The percentage mass below the diameter of interest is the number expressed after the "D". The D10 diameter is the diameter at which 10% of a sample's mass is comprised of smaller particles, the D50 is the diameter at which 50% of a sample's mass is comprised of smaller particles, and the D90 is the diameter at which 90% of a sample’s mass is made up of smaller particles.
Importance of particle size distribution?
The importance of particle size analysis in pharma manufacturing is significant. Knowing the PSD is highly important as it allows for far greater process control. With increased control, dissolution rates, drug uniformity, drug bioavailability, and quality targets can be achieved more easily.
How to determine particle size?
D-values are relatively simple to compute but are challenging to determine for a real product in real-time. The main obstacle is quantifying the size of the particles.
A novel method to determine particle size is direct imaging, like our Eyecon2 Particle Size Analyzer. In direct imaging, particles are illuminated and imaged from the same side. This allows the method to be easily used both in bench-top and in-line applications.
A major advantage of this method is it non-invasive with no product contact and it is non-destructive. Direct imaging affords greater flexibility with adjustable max and min diameters to shape measurement detection and it negates false detection of shadowing particles, where small fine particles hide in front of larger particles.
How to calculate particle size?
While D-values are based on a division of the mass of a sample by diameter, the actual mass of the particles or the sample does not need to be known. A relative mass is sufficient as D-values are concerned only with a ratio of masses. This allows the optical measurement systems to be used without any need for sample weighing. From the diameter values obtained for each particle a relative mass can be assigned.
Assuming that ρ is constant for all particles and cancelling all constants from the equation:
Each particle's diameter is therefore cubed to give its relative mass. These values can be summed to calculate the total relative mass of the sample measured. The values may then be arranged in ascending order and added iteratively until the total reaches 10%, 50% or 90% of the total relative mass of the sample. The corresponding D-value for each of these is the diameter of the last particle added.
For more information on particle size determination using direct image analysis, get in touch!