Predicting Handling Behaviour For High-value Powders

The drive towards sustainable manufacture and reduced carbon footprints has increased the need to maximise process availability whilst simultaneously reducing the generation of out of specification powder-based products. 

This increasing drive has led to much research and advancement in test techniques to predict production line performance from the analysis of increasingly small scale samples. 

This particular requirement is of great significance for manufacturing processes that handle high value, high potency powders or for material that is being developed at the formulation stage of its commercial life cycle. 

Powder flow property

The powder flow property is an essential bulk property in powder handling manufacturing processes because it helps to ensure that the processes are effectively managed and that a constant level of product quality can be maintained.

Powder flow can have a particularly significant impact on the degree to which active ingredients are distributed uniformly across different formulations. It is common practice to design a formulation without taking into account problems in the manufacturing process that are brought on by the poor flowability of the raw components. This could result in major variances in the content homogeneity, which in turn could lead to products that do not meet their specifications.

Powder flowability should be thoroughly understood early on in the process of developing a new product in order to make informed decisions on the production approach (for example, direct compression versus wet granulation) and the formulation (e.g., powder loading).

The ‘conventional’ scientific evaluation of powder flow, on the other hand, necessitates the collection of a sizeable number of powder samples in order to reliably measure properties using a standard shear cell tests (15g minimum per test).

The amount of sample material needed for ‘conventional’ shear cell testing can be significant, in terms of value or availability in certain cases. However, the quantity of a new formulation that is typically available during the early stages of the development process is on the scale of grammes.

Evaluating powder flowability

In the early stages of product development, it would be extremely beneficial to conduct an evaluation of the powder's flowability using only a very tiny amount of the powder. A new method that has been developed at the Wolfson Centre is able to predict powder flowability solely based on the material's physical properties and cohesiveness, which are represented by measuring the Bond Number using milligrams of powders.

This new method was developed to improve the accuracy of previous predictions. The method operates under the presumption that a small sample of powders (typically less than one hundred milligrams) contains sufficient particles to represent distributions of sizes, shapes, and contact orientations.

This allows for measurements to be taken that can capture the stochastic effects of particle morphology, surface chemistry, and bulk behaviour. Although the model has been successfully applied to a wide variety of components, it is not yet known how well the predictions align with the findings of the numerous kinds of shear cell tests that are typically carried out in the manufacturing sector.

Measuring particle adhesion force

In this study, a mechanical surface energy tester (shown in Fig 1) was used to measure the particle adhesion force for determining the Bond number. In the measurements, a standard disc made of glass was used as a substrate surface instead of a powdered substrate due to its small influence on the results. In the tests, about 50 mg of a sample powder was dispersed onto the substrate using an air expansion disperser operated at a pressure of 1.5 bar.

The sampled substrate was weighed to measure the mass of the dispersed sample powder using a digital balance (accuracy of 0.1 mg). The substrate disc was fitted onto a carriage that could slide down along a guide rod under gravity and stop against a metal buffer to create a measured deceleration of the particles.

The mass of the powders detached from the disc was measured using a digital balance. The acceleration and the mass (50% detached from the total dispersed particles) were used for the calculation of the F_ad and the Bo in Eq. (1) at the particle size measured using Mastersizer 3000.

A wide range of powders has been selected for this study, including calcium carbonate, lactose, microcrystalline cellulose, paracetamol, ibuprofen, and titanium dioxide giving a wide range of material properties such as particle size and particle density.

The accelerations measured for all sample powders are presented in Fig. 2, which shows the mass percentage of the detached material over the total material deposited versus the acceleration needed for the detachment. Correspondingly, the bond number was calculated as described in Equation 1.

Powder flowability of the sample powders has been measured using the PFT as shown in Figure 3. With the data, correlations between the flowability and the bond numbers of the powders were explored. Based on the correlations that were uncovered, a prediction model of powder flowability was developed and the model was validated using data that was not used for the modelling development as shown in Fig 3.

Validations of the model show that the prediction model has a good agreement with the experimental data measured using a PFT tester. The results follow the same trends as the shear cell tester gives. Therefore, the model shows a great advantage because the model allows assessing powder flowability using a few milligrams of the sample.

Powder by Design

The results show that this novel test method can directly measure the forces with which particles adhere to each other, using a small sample (milligrams) of a particulate substance. The measurements from the novel test have demonstrated a strong predictive capability for assessing the real challenges of handling the substances at the manufacturing scale, particularly for flow properties of the powders.

This will enable the formulation to be adjusted for optimisation for manufacturing at an early stage (Powder by Design) or production lines to be chosen or designed for trouble-free start-up (Process by Design) at a much earlier stage.

The consequent reduction of processing problems during scale-up to manufacturing will enable reduced time to market, improving profitability and early social impact of new chemical entities (NCEs) and formulations.