Transforming Pharmaceutical Manufacturing Advanced Techniques for Enhancing Powder Mixing Productivity Revealed
Authors: - Shalini Sharma , - Deovrat kumar , - Preeti , - Akshay Sharma 
Published: September 2024

In the production of pharmaceuticals, powder mixing is an essential step that guarantees the consistency of powder formulations (drugs and excipients) prior to their conversion into capsules or tablets. Currently, an empirical trial-and-error methodology is extensively relied upon for powder mixing process modifications and scale-up. The goal of this thesis is to replace this haphazard approach more methodical design-based one.
Prior studies have demonstrated that the combination of 1% red iron oxide tracer and 99% lactose powder causes a characteristic color change, going from pink to red and finally to orange. Similar color points in tumbler, high shear, and mechanofusion mixers have been validated by spectrophotometric measurement, and this color shift has been seen in a variety of mixer types (for example, the blend color at 45 minutes in a tumbler matches that at 20 minutes in a high shear mixer). This thesis aims to explore the potential of the color tracer method and its applicability in the pharmaceutical industry. The accuracy of the color tracer method was reviewed in the first chapter, showing its resilience with little variation in color when mixed. Additionally, it was found that 0.5–1% was the ideal concentration and that various mixer types—such as tumblers and high shear mixers—produced color endpoints that were constant and made for useful comparisons. Furthermore, different lactose types were found to display their distinct color curves. Testing various iron oxide tracers, such as the red, purple, black, and yellow varieties, was covered in detail in the second chapter. Because of its stability at mixing temperatures, small particle size for efficient powder coverage, low concentration requirements, and wide color range during mixing, red iron oxide turned out to be the best option. This chapter also shed light on the peculiar color change of the red iron oxide-lactose mix, explaining that it is caused by the orange color of the individual red iron oxide primary particles, which gives rise to the final orange blend. Previous studies on iron oxide color particles revealed that the characteristic orange hue is caused by the size and shape of the particle scattering particular light wavelengths. The third chapter expanded the application of the color tracer method by testing it with various white organic excipient powders besides lactose, including HPMC, MCC, mannitol, and PVP. These excipients displayed similar blend color changes but exhibited their unique color curves, demonstrating the versatility of the color tracer method.
The fourth chapter investigated the possibility of predicting the mixing time point for content homogeneity in the Ventolin formulation using the color tracer approach. The comparison of equivalent blend color points from two distinct mixers—high shear and tumbler—was used to arrive at this conclusion. The color tracer method may be a workable way to scale up mixing procedures, according to the results.
In conclusion, the findings in this thesis provide strong support for the adoption of the color tracer method in powder mixing within the pharmaceutical and solids mixing industries. This innovative approach has the potential to revolutionize the scale-up process and move away from the traditional trial-and-error method.