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The Effects of Particle Size Distribution on the Properties of Medical Materials

Author: Matthew Cantelo

This work by Ceram is licensed under a Creative Commons AttributionNonCommercial-ShareAlike 3.0 Unported License

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Introduction
As so many 3-D products are created from powder particles, the shape and size of these particulates can have a great impact on the physical and chemical properties of the final product. Analysis of the size distribution and shape of the particles can also give useful information concerning the processes they go through in manufacturing, and can help make these processes more efficient as well as, of course, helping to solve problems. This is of particular importance in the field of medical materials and devices, as processing control for materials that enter the body is vital. This white paper will discuss laser diffraction, a well-known method for measuring particle size distribution (PSD). As well as describing the theory behind it, the paper will focus on how important laser diffraction can be to the field of medical materials.

The Importance of PSD Measurements


The distribution of particle sizes in glass, ceramic, metal and polymer powders is of vital importance to many industries, ranging from the medical to aerospace and construction sectors. Many raw material producers, and their clients also, employ processes like milling to create a target powder size or shape. Given that powders often represent the starting point in production, it is important to ensure that both the powder supplier and user are confident that a desired size distribution is being consistently achieved. There are two aspects to this: consistent processing and consistent measurement of particle size. Both require the definition and compliance with SOPs (Standard Operating Procedures). If this has not been achieved, the powders will not perform as expected, causing (a) time wasted in supplier-end-user disputes concerning the nature of powder supplied and/or (b) poor yields/increased waste at different process steps and/or (c) variable end-product performance and the risk of customer dissatisfaction or even legal action. There are several different methods available for measuring the size of particles. These range from simple techniques such as sieve analysis or use of optical microscopes through to techniques based on sedimentation rates as a function of particle size. At Ceram we tend to rely on using the Malvern Mastersizer 3000 to measure sizes using a laser diffraction technique. This method is suitable for a wide variety of materials in the particle size range <10m to more than 100m, and Ceram has experience with characterising everything from sand and clays to medical-grade implant coatings. The theory behind this measurement method, and the practical aspects of the technique, will now be discussed.

Figure 1 A Typical Particle Size Distribution Curve 2


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The Experimental Procedure


The powder sample under investigation is mixed to obtain a representative sample. This can be done, for example, by a method called cone and quarter, where the sample is shaped into a cone, flattened, and divided into four equal sections. One of these sections is taken and the process is repeated until only 1/16th of the original volume is left. Other techniques include riffling and scoop sampling2. The apparatus can now be filled with the dispersant a liquid that will not affect the physical or chemical properties of the powder, but simply allow it to be transported from the reservoir cell into the detector apparatus. For example, hydroxyapatite would be dispersed in water as it is insoluble in it, but certain silicate-based glasses would be dispersed in ethanol as these would dissolve in the water. It should be noted that the term dispersant should not be confused with surfactants - in this case, it is just a liquid medium to transport the suspended particles. The apparatus must be flushed through with the clean dispersant of choice before any experiments are performed, and the detector window aligned and the background measured. Measuring the background greatly improves the signal-to-noise ratio, making the measurements as accurate as possible. This is all done with constant stirring of the dispersant, and the system should be allowed to settle and thermally equilibrate before any background measurements and alignment takes place3. The system pre-sets now need to be set up using the PC software. Each dispersant has a pre-set refractive index, and this is used in conjunction with the particles refractive index to calculate the distributions. Most substances have a value already in the database, but if necessary values can be allocated from data in the literature. For almost all wet samples, the pre-sets for non-spherical particles can be used, and measurements are programmed to be taken at set time intervals (usually a few seconds apart), alternating between the blue and the red lasers. The different wavelengths of light give different scattering from the particles, to obtain a full range of values from the detectors in the Mastersizer (see later). An acceptable obscuration range is also programmed, and a suitable analysis model is chosen to fit with the type of particle. The representative powder sample is now added, small amounts at a time, until the obscuration is in a suitable range. Finer particles need a lower obscuration to produce accurate results compared to more coarse particles, but an obscuration in the range 4 15% will give more accurate results as this reduces the signal-to-noise ratio. When considering how the powder sample is introduced, the following is worthy of note: Direct addition of powder may mean the introduction of agglomerates that take a long time to break down. As an alternative, powders can be pre-dispersed in the dispersant. However, if the resulting dispersion is dilute, using a pipette to subsequently add sample can mean coarser particles are left behind as a sediment (leading to a spurious PSD with a misleadingly high contribution from finer particles). Therefore creation of a homogeneous paste may be the best approach. Measurements can now be taken, and will be produced as a report in the software. A good practice is to take two sets of measurements several minutes apart, as this can highlight any de-agglomeration or agglomeration that may be taking place in the system. Ultrasonics can be employed to break up any agglomerations, and so a true measurement of the PSD can be obtained, rather than an inaccurate one. Alternatively surfactants can help ensure deflocculation and so give a true measure of primary particle size distribution. The data is presented as a distribution curve, an example is shown in figure 1. The key values from the report are the size value at the highest point of the curve the
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modal particle size, and the d10, d50 and d90 values. These values represent the sizes (in microns) at which 10%, 50% and 90% of the total particles has a smaller size, and are often used as standards in QC work. The second green line is the cumulative volume, which shows the amount of particles in total that are under any given size. It is important to appreciate that these curves can also take the form of volume or number distributions, and care needs to be taken when selecting which to use. If particle size is small, e.g. sub-micron level, then a number distribution will provide more accurate information as each particles contribution to the overall volume is small. Conversely for larger particles, a volume distribution would give more accurate results4.

Laser Diffraction The Theory


Measuring particle size with laser diffraction typically employs two different wavelengths of light a red laser, in the region of 700nm, and a blue laser in the region of 470nm. When the particles are brought through the laser beams with the dispersant, the light is scattered by the particles and picked up by a range of detectors around the measuring cell. Smaller particles have a larger scattering angle, whereas larger particles have a smaller scattering angle. Cerams apparatus has a ring of 63 detectors around the measuring cell, with detector 1 being in front of the sample and detector 63 effectively behind the sample, for those particles with the widest scattering angles. These can be viewed in real time using the PC software. As mentioned above, a large particle will give a small scattering angle and this will be picked up by the lower number detectors, and small particles with the larger scattering angles will be picked up by the higher number detectors.

Incident Light

Small Particle Large Scattering Angle

Incident Light

Large Particle Small Scattering Angle

Figure 2 Particle Size and Scattering Angle

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Once the measurements have been taken, a mathematical process based on the Mie theory takes these values and predicts the scattering of light at all possible angles. According to ISO13320-1, this is the best method for particle sizes less than 50m (below sieve measuring limits). Another theory that was widely used, the Fraunhofer approximation, only accounts for classical diffraction around the particles and assumes that they are opaque, whereas the Mie theory takes the refractive index of the particle into account. The Mie theory requires knowledge of the particle and dispersant refractive indices, as well as the imaginary particle refractive index, all of which can be obtained from the apparatuss database. If a materials RI values are not listed, the values can be estimated and then edited later on depending on their fit with the data. There needs to be good agreement between the so-called residual values, the difference between the actual measurement and the predicted data. However, it must be noted that a good data fit does not necessarily give a correct result4.

Variability in PSD Investigations


The importance of having a thorough protocol for measuring PSDs and ensuring all the relevant information needed for the processing of the values was highlighted in a round robin study performed by the National Physical Laboratory (NPL) in conjunction with Ceram and Leeds University5. Samples of crystalline silica were sent to different laboratories, one with a known median particle size of <10m (A) and one with a known size of <100m (B). Minimal information was provided with the samples but partner labs were encouraged to answer questions concerning the methodology they had selected in undertaking the analysis. This was repeated a year later, the difference being that partner labs were additionally supplied with more thorough procedures and methods to use. Unknown to the labs, the same samples (labelled C and D this time) were sent. The results of this investigation show clearly that once the procedures and thorough protocols have been put in place, the agreement between the measurements made at different labs improved and the coefficient of variation was greatly reduced in nearly all of the cases. This coefficient decreased more for the larger silica particle size. The standard deviation for the A samples was also larger than that of B, indicating that free reign over the method used, without questioning, does not necessarily give an accurate result (comparing A and B against C and D). This study highlights the importance of using thorough methods and strict sampling protocols to obtain accurate results, but also that measurements can vary significantly between laboratories depending on the protocols they use. The results may be accurate according to their standards, but not necessarily the correct results2. It is very common for clients to come to Ceram asking for particle size distribution tests to be performed on a powder with no prior information on test protocols provided, which can lead to discussions around the results, despite the measurements being performed as accurately as possible according to a standard inhouse protocol. This highlights the importance of working with clients to develop a protocol specific to their materials, something Ceram is very capable of. We have extensive experience in the fields of powder processing and characterisation, and this expertise can help provide the most accurate and reproducible data between laboratories. Very relevant to this process is understanding how powder samples behave in water: many problems arise from the fact that powders have a low surface charge in water and so a strong tendency to agglomerate. Particle size measurements then often reveal additional coarse peaks that are not representative of the primary particles. This can be rectified through changes to suspension pH or the use of surfactants. The interested reader is encouraged to read this white paper
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in conjunction with previous ones - The Role of Zeta Potential in the Manufacture of Healthcare Materials and The Applications of Zeta Potential in Process Control on the Ceram website. An example of the link between zeta potential and PSD is shown in some testing work carried out for a client on titania powders. The initial experiments showed that the titania particles were flocculating and giving a misleading merged bi-modal distribution. After conducting zeta potential vs pH measurements and then mixing in a small amount of a suitable anionic surfactant, PSD measurements gave a distribution with one, much sharper peak at the lower particle size rather than two. The surfactant had the effect of increasing the surface charge of the particles, and subsequently their zeta potential. This meant that the particles possessed enhanced electrostatic repulsions (versus Van Der Waals forces) leading to no flocculation6.

PSD Measurements and the Medical Sector


PSD measurements are important to many industry sectors, but become even more important when applied to materials that have medical applications and will be used in the body. The processing of these materials must be even more tightly controlled than in other industries, as they are subject to a huge range of regulations (e.g. the Food and Drug Administration, FDA). Two very important classes of biomaterials that Ceram has experience in manufacturing are hydroxyapatites (HA) and bioactive glasses. Both of these materials are widely used as implant coatings, conferring increased bioactivity, solubility, or releasing ions or organic molecules to the body for therapeutic purposes or to promote integration with existing bone. These materials can be coated onto an implant - usually made from a titanium alloy - by plasma spraying of a spray-dried granulate form of HA or bioactive glass. During spraying, where the coating is subjected to very high temperatures as it passes through the spray gun. This ensures it assumes a plasticity so that it splats onto the metal substrate. Returning to the start of the process, obtaining the correct particle size distribution in the primary HA powder is crucial for this process: particle size distribution will impact on the rheology of the slurry and therefore the solids loading. This, in turn will alter the granulate morphology and size distribution after subsequent spray drying. If the particles are too small in the primary powder suspension, they will remain this way during the spray-drying process as well. They will have a tendency to move closer together and the resulting static effects will result in intermittent spraying. If the particles are too large then there is the possibility of blocking the spray drying nozzle. The ideal situation therefore is a very narrow particle size distribution around a specific size range, typically 50-70m, and this will give a suitably even and consistent coating7, 8.

Conclusion
While it may seem initially like a relatively simple routine characterisation test, measuring the particle size distribution of a solid powder can be challenging. When performed correctly however, it can give a lot of information that informs powder processing and so end-product performance. This is vital for a wide range of industries, and Ceram can help ensure that clients materials are of the right specification for their needs.

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References
1. Work done at Ceram in 2013 for a client, investigating the particle size distribution of a range of different biomaterials. 2. Good Practice Guide for Improving the Consistency of Particle Size Measurement, K Mingard, R Morrell, P Jackson, S Lawson, S Patel and R Buxton, National Physical Laboratory Publications (2009) 3. Malvern Instruments MS3000 Customer Training Course, Part 1 Basic Principles and Data Quality (2012) 4. Malvern Instruments MS3000 Customer Training Course, Part 2 Obtaining and Understanding the Size Distribution (2012) 5. Malvern Instruments MS3000 Customer Training Course, Part 3 Method Screening, Wet Measurements (2012) 6. Work done at Ceram in 2012 for a client, investigating the particle size distribution of titania suspensions. 7. P. Chean and K.A. Khor, Biomaterials 17 (1996) 537-544 8. M. Monsalve, H. Ageorges, E. Lopez, F. Vargas, F. Bolivar, Surface and Coatings Technology 220 (2013) 6066

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About Ceram
Ceram is an independent expert in innovation, sustainability and quality assurance of materials. With a long history in the ceramics industry, Ceram has diversified into other materials and other markets including aerospace and defence, medical and healthcare, minerals, electronics and energy and environment. Partnership is central to how we do business; we work with our clients to understand their needs so that we can help them overcome materials challenges, develop new products, processes and technologies and gain real, tangible results. Headquartered in Staffordshire, UK, Ceram has approved laboratories around the world.

About the Author


Matthew Cantelo Laboratory Chemist Matthew Cantelo has a MChem (Hons) chemistry degree from Cardiff University. His final year research project was largely focused on inorganic synthesis within healthcare applications. This is an area that Matthew is continuing to concentrate on at Ceram, particularly with regards to hydroxyapatite synthesis.

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