Uniaxial Powder Testing for Optimizing High Shear Wet Granulation

In order to assess and rank powder flowability for a large scope of powder handling processes in various industries, including construction, pharmaceutical, chemical and  food, uniaxial Unconfined Yield Strength (uUYS) can be employed.

This article outlines a study which uses the Uniaxial Powder Tester (UPT) to characterize a range of pharmaceutical blends and the corresponding granulates to show how uUYS values can clearly differentiate between the formulations and quantify the effect of the granulation process conditions.

Uniaxial Powder Testing for Optimizing High Shear Wet Granulation

Image Credit: Freeman Technology

The first step in uniaxial testing involves the construction of a powder column at a given Major Principal Stress (MPS or σ1), next the confining sleeve is removed and the freestanding column of material is fractured.

The force which is needed to break the column shows on the uUYS (σC) of the powder. The UPT also permits bulk powder properties such as compressibility and density to be established.

Consolidation studies may also be performed in a number of environments by utilizing an off-instrument Consolidation Station. Samples may be consolidated at a specific humidity and/or temperature for extended periods of time.

Uniaxial Powder Testing for Optimizing High Shear Wet Granulation

Image Credit: Freeman Technology

Experimental Set-Up

 

Mixtures which contain different ratios of microcrystalline cellulose (MCC) and lactose were dry mixed for 3 minutes in a turbula mixture (total powder volume 750 ml). The resulting dry mixtures were then put through a wet granulation process, where the volume of water necessary was added over 90 seconds.

The powder was pre-consolidated at 8 kPa for 5 seconds during uniaxial testing. Using a unique double-ended compaction technique, an MPS of 40 kPa was then applied for 30 seconds before the uUYS was measured, alongside the compressibility, Poured Bulk Density (BDP), and Consolidated Bulk Density (BDC).

The first part of this experiment assessed a 50:50 mixture of lactose and MCC with varying levels of water content utilized throughout granulation. The second phase looked at differing ratios of lactose: MCC with fixed 40 % water content.

For a further 180 seconds the granulation process was continued and the resulting wet mass was then screened through an 850 µm sieve, dried at 60 °C for 7 hours and then re-screened through a 2 mm sieve.

Dry Mix % Water
% Lactose % MCC
15 85 0, 40
30 70 0, 40
50 50 0, 10, 20, 30, 40
70 30 0, 40
85 15 0, 40

Source: Freeman Technology

The powder was pre-consolidated at 8 kPa for 5 seconds during uniaxial testing. Using a unique double-ended compaction technique, an MPS of 40 kPa was then applied for 30 seconds before the uUYS was measured, alongside the compressibility, Poured Bulk Density (BDP), and Consolidated Bulk Density (BDC).

The first part of this experiment assessed a 50:50 mixture of lactose and MCC with varying levels of water content utilized throughout granulation. The second phase looked at differing ratios of lactose: MCC with fixed 40 % water content.

Results – Water Content

The following findings relating the flow properties of the dry mix and granules were demonstrated:

  • The Dry Mix of 50:50 lactose: compared to the raw components of MCC and lactose, MCC showed intermediate behavior.
  • A visual assessment of the wet mass suggested that granule formation started at 30 % water content and became dominant at 40 %, as can be seen in the optical microscopy images.
  • Even at 10 % content, the addition of water led to a decrease in uUYS, suggesting better flow for the granules compared to the dry mix. This is probably because of a reduction in fines and/or changes in surface properties.
  • A clear correlation exists between water content and flow properties with uUYS continuing to decrease with increasing water content, indicating further improvements in the flow properties of the granules.
  • Compressibility shows a similar but less pronounced trend, suggesting enhanced packing efficiency as water content increases.
  • Generally, a similar trend is seen with the density measurements, with the exception of 40 % water content where BDP and BDC values show slight increases, possibly because of granule densification.
Uniaxial Powder Testing for Optimizing High Shear Wet Granulation

Image Credit: Freeman Technology

Result – Excipient Ratio

Uniaxial Powder Testing for Optimizing High Shear Wet Granulation

Image Credit: Freeman Technology

Some clear correlations were seen between the flow properties of the dry mix and corresponding granules with increasing lactose content:

  • Compressibility increases as lactose content increases for the dry mixes. Higher compressibility usually correlates with greater cohesion. An inverse trend is seen for the granules. Therefore, measuring compressibility alone does not sufficiently or accurately inform on the flow properties.
  • For both the dry mixes and granules there is a decrease in uUYS with increasing lactose content, which suggests that a higher lactose content leads to a less cohesive formulation. Interestingly, the alteration in uUYS with respect to lactose content is not linear for the granules. So, the properties of the granules cannot be predicted from knowledge of the raw components alone.
  • The uUYS for the granules is lower than that of their dry mix counterpart. This shows the effectiveness of the granulation process, and the UPT’s ability to calculate the effect of the process.
  • BDC and BDP for the granules remain relatively consistent. So, density is not a reliable differentiator and supplies limited information on the behavior of the samples.

Conclusions

The data reveals the high sensitivity and repeatability of the UPT, allowing the influence of formulation and process alterations to be measured. Compared to the dry mix, the granules displayed a consistent improvement in flow.

Clear trends were seen between excipient formulation, water content, and the flow properties of the resulting granulate. Increasing lactose or water content decreased both uUYS and compressibility of the resulting granules.

The advantages of uniaxial powder testing can now be utilized in industrial applications.  A reliable, robust, and simple uniaxial tester which can construct consistent, free-standing powder columns from a large scope of commonly used powders, means that even inexperienced users can acquire precise and repeatable results.

Those looking for a quick and reliable technique for troubleshooting process issues, or fast screening of raw materials, intermediates and finished products, now have an additional and more cost-effective choice.

This information has been sourced, reviewed and adapted from materials provided by Freeman Technology.

For more information on this source, please visit Freeman Technology.

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