Introducing the Mastersizer 3000+

The introduction of the Mastersizer 3000+ presents many exciting opportunities for scientists and researchers interested in particle size analysis.  

Software features in the new Mastersizer Xplorer software such as SOP Architect and Data Quality Guidance make developing methods and generating the best quality data easier than ever. Whilst Size Sure, which uses Malvern Panalytical’s patent-pending Adaptive Diffraction technology, represents a new direction for laser diffraction and will help to improve measurement reproducibility. 

The Mastersizer optical bench has also been upgraded with an innovative solution to help with internal heat management. The benefit? Significantly reduced time for dispersant stabilization when working with more challenging dispersants such as propanol and iso-octane. Spend less time waiting around to start testing and more time generating the data you need.

Method Transfer 

However, we appreciate that some might wonder about transferring methods from the Mastersizer 3000 to the Mastersizer 3000+. Method transfer during an instrument upgrade can be a costly and labor-intensive process. The following questions might come to mind:

• Is it an easy process to transfer methods from the Mastersizer 3000 to the Mastersizer 3000+?
• Will my old measurement files and SOP files work with the new software, Mastersizer Xplorer?
• Will I achieve equivalent data for the same sample on the Mastersizer 3000 and Mastersizer 3000+, if I use the same method?

Well, Malvern Panalytical are pleased to say that the answer to all three questions is ‘YES!’. Method transfer from the Mastersizer 3000 to Mastersizer 3000+ is effortless. Historic measurement and SOP files can be opened and used in Mastersizer Xplorer, and crucially equivalent data for your samples can be generated on the Mastersizer 3000+ when you are using your Mastersizer 3000 methods.

Data Equivalence

During the development of the Mastersizer 3000+, we have conducted a suite of tests to demonstrate equivalency between the Mastersizer 3000 and Mastersizer 3000+. These tests fall into two categories:

• Reference materials
  Tests with latex samples at nominal sizes of 60, 100, 151, 401, 702, 994 and 8900 nm. These are the same production tests that each and every Mastersizer 3000 or Mastersizer 3000+ optical bench must pass before it can be released for shipment to a customer. This set of latex samples covers the full scattering range of the Mastersizer 3000 and 3000+ instruments. 
  
  
• Real life samples
  Tests with typical real life samples including alumina, silicon dioxide, ibuprofen and lactose. These samples cover a wide range of sizes and required operating conditions including different dispersants. 

These tests are a form of reproducibility assessment, whereby we are testing the precision between two instrument generations. Both USP and European Pharmacopoeia recommend acceptance criteria for reproducibility testing of a percentage relative standard deviation (%RSD) of less than 10% on Dv50 or any similar central value and less than 15% on values toward the edge of the distribution such as Dv10 and Dv90. For any samples containing particles smaller than 10 µm, these limits can be doubled. 

An alternative set of criteria for consideration are those for method repeatability assessments from ISO 13320:2020, namely: 

• The Dv10 from each test shall not deviate from average value of the 6 measured results values by more than ± 3%.
• The Dv50 shall not deviate from average value of the 6 measured results values by more than ± 2.5 %.
• The Dv90 shall not deviate from average value of the 6 measured results values by more than ± 4 %.

However, ISO 13320:2020 is predicated on the wet or dry dispersion measurements having been carried out on one instrument only, which is not the case in this exercise. 

Reference Materials

When performing particle size analysis, there are three main sources of measurement uncertainty:

• Sampling related 
• Dispersion related
• Instrument related

For the purposes of demonstrating equivalence between the Mastersizer 3000+ and Mastersizer 3000 optical benches, we must ideally minimize the uncertainty associated with sampling and dispersion of any samples used. With these sources of uncertainty successfully minimized, we can be confident that any differences are associated with the instrument(s). 

Latex samples are ideal for this purpose; they are homogeneous and easily dispersed, so measurement uncertainty associated with sampling and dispersion is significantly diminished. The other benefit is that they are well-characterized and NIST traceable with known size specifications. 

As part of this exercise, 33 Mastersizer 3000+ Ultra optical benches and 33 contemporary Mastersizer 3000 optical benches were assessed. Like-for-like standard test conditions were used when testing each latex sample, including like-for-like dispersion accessories. A single aliquot of each latex sample was tested per optical bench. 

Table 1 summarises the mean Dv10, Dv50 and Dv90 values for each latex sample across the 33 Mastersizer 3000 optical benches and the 33 Mastersizer 3000+ optical benches. The percentage difference between results from the Mastersizer 3000 and Mastersizer 3000+ is also reported. 

Table 2 summarises the percentage relative standard deviation (%RSD) for each latex sample achieved across the 33 Mastersizer 3000s and 33 Mastersizer 3000+s. The percentage difference between results from the Mastersizer 3000 and Mastersizer 3000+ is also reported. 

Table 1: Mean particle size data for latex samples on Mastersizer 3000 and Mastersizer 3000+

Table 2: % Coefficient of Variation (CV) data for latex samples on Mastersizer 3000 and Mastersizer 3000+ 

The results in Table 1 demonstrate that the sizes reported by the Mastersizer 3000+ and Mastersizer 3000 are highly similar for all latex samples tested. In all cases, the percentage difference is below 1 %. The %RSD values for all latex samples on the Mastersizer 3000 and Mastersizer 3000+ are also very low, showing that the Mastersizer 3000+ delivers excellent measurement reproducibility just as the Mastersizer 3000 did. 

Real Life Samples

The latex sample data is very clear in demonstrating that the size measurement capabilities of the Mastersizer 3000 and Mastersizer 3000+ are equivalent. However, latex samples are not representative of the full variety of samples that Mastersizer users wish to analyse. As such, we have also performed testing on several ‘real life’ samples with broader size distributions and which require different test conditions. 

Alumina, silicon dioxide and ibuprofen samples were tested in water. A lactose LH200 sample was also tested in iso-octane, which is one of the dispersants where significant time savings can be observed with the Mastersizer 3000+. With the LH200 sample, we are demonstrating that the heat management system within the Mastersizer 3000+ has no impact on recorded size results, despite it making a positive impact with the reduction of the dispersant temperature and time required for equilibration. 

For all samples, an expert user developed an optimized method for the sample using the Mastersizer 3000 optical bench before completing the equivalency testing. 

Alumina (in water)

Three aliquots were tested with one Mastersizer 3000 optical bench and one Mastersizer 3000+ Ultra optical bench. For each aliquot, 10 records were generated and averaged. Water was used as the dispersant within a Hydro MV accessory. 

Table 3 summarises the average Dv10, Dv50 and Dv90 result from each sample aliquot tested on the Mastersizer 3000 and Mastersizer 3000+ optical benches. Overall mean values are also calculated, as well as standard deviation and %RSD across the six averaged results. 

Figure 1 shows an overlay of the average particle size distributions (PSDs) generated for each aliquot tested on the Mastersizer 3000 and Mastersizer 3000+ optical benches. 

Table 3: Mean particle size data for alumina sample on Mastersizer 3000 and Mastersizer 3000+

Figure 1: Overlay of mean particle size distributions for alumina sample on Mastersizer 3000 and Mastersizer 3000+

The %RSD values are significantly lower than both the USP <429>/Ph. Eur. 2. 9. 31. and ISO 13320:2020 criteria, and the PSDs overlay. 

Silicon dioxide (in water)

Three aliquots were tested with one Mastersizer 3000 optical bench and one Mastersizer 3000+ Ultra optical bench. For each aliquot, 10 records were generated and averaged. Water was used as the dispersant within a Hydro MV accessory. 

Similar data sets are shown for this sample in Table 4 and Figure 2. 

Table 4: Mean particle size data for silicon dioxide sample on Mastersizer 3000 and Mastersizer 3000+

Figure 2: Overlay of mean particle size distributions for silicon dioxide sample on Mastersizer 3000 and Mastersizer 3000+

The %RSD values are significantly lower than the USP <429> /Ph. Eur. 2. 9. 31. criteria and the PSDs overlay. The %RSD for the Dv90 is slightly higher due to the presence of tightly bound agglomerates and/or aggregates, which could not be dispersed and gave rise to a secondary mode at larger particle sizes. The %RSD values also meet the ISO 13320:2020 criteria.

Ibuprofen suspension (in water)

Three aliquots were tested with one Mastersizer 3000 and one Mastersizer 3000+ Ultra optical bench with Hydro MV accessories. For each aliquot, 10 records were generated and averaged. Water was used as the dispersant. 

Similar data sets are shown for this sample in Table 5 and Figure 3. 

Table 5: Mean particle size data for ibuprofen suspension sample on Mastersizer 3000 and Mastersizer 3000+

Figure 3: Overlay of mean particle size distributions for ibuprofen suspension sample on Mastersizer 3000 and Mastersizer 3000+

The %RSD values meet the USP <429>/Ph. Eur. 2. 9. 31.  and ISO 13320:2020 criteria and the PSDs overlay. 

Lactose LH200 (in iso-octane)

A single aliquot was tested with one Mastersizer 3000 and one Mastersizer 3000+ Ultra optical bench with Hydro MV accessories. Equal pre-measurement delays of 180 seconds were applied on Mastersizer 3000 and Mastersizer 3000+ before reported data was acquired. This ensured that the dispersant temperature had stabilized in each and thermal artifacts were effectively eliminated. For each aliquot, 10 records were generated and averaged. Iso-octane was used as the dispersant. 

Similar data sets are shown for this sample in Table 6 and Figure 4. Percentage difference has been calculated in this case. 

Table 6: Mean particle size data for lactose LH200 sample on Mastersizer 3000 and Mastersizer 3000+

Figure 4: Overlay of mean particle size distributions for lactose LH200 sample on Mastersizer 3000 and Mastersizer 3000+

The % difference values meet the USP <429> /Ph. Eur. 2. 9. 31.  and ISO 13320:2020 criteria and the PSDS overlay. 

Conclusions

Reference samples and real-life samples have been tested to demonstrate data equivalency between the Mastersizer 3000 and Mastersizer 3000+ Ultra optical bench. ISO 13320:2020 and USP <429> /Ph. Eur. 2. 9. 31. criteria have been used as part of this assessment. In all cases, the recorded data met the acceptance criteria and showed excellent reproducibility between the two generations of Mastersizer.