Issue link: https://www.e-digitaleditions.com/i/1112785
Tablets & Capsules May 2019 19 in the percentage of particles smaller than 40 microns when exposed to various stress-strain conditions. Likewise, Figure 3 describes the increase in the per- centage of particles smaller than 160 microns when exposed to various stress-strain conditions. In pharmaceutical tableting processes, unwanted particle breakage can lead to segregation, weight vari- ation, and poor compaction, resulting in 10 to 20 per- cent product loss during a production run or time-to- market delays as engineers attempt to fix the problem and pass process validation requirements. Time-to- market delays can cost a pharmaceutical company mil- lions or even billions of dollars, depending on the drug product. Particle breakage can also cause a free-flow- ing material to become cohesive and hang up in pro- cess vessels, which may require expensive retrofits to ensure adequate flow. In this article, I'll provide a systematic and sci- ence-based approach for solving, or at least under- standing, the problem of unwanted particle breakage. The basic steps of the approach are: • Test the material and measure breakage due to stress, strain, and impact conditions; • Compute the stress, strain, and impact in process equipment; • Quantify the particle breakage occurring in each region of process equipment; and • Modify the process to mitigate the particle breakage. Testing and measuring particle breakage Processing and handling can break particles by three mechanisms: stress-strain events, impact events, or shear-cutting events. In this article, I'll limit the dis- cussion to stress-strain and impact events. To understand the magnitude and cause of breakage for a material, you must test the material and measure the amount of breakage caused by each type of event. Ideally, you should use test methods that only measure breakage from a single type of event, either stress- strain or impact. This isolates effects of breakage due to one mechanism or the other. Stress-strain breakage. You can measure breakage due to stress-strain events using a special shear device that is significantly different from a typical shear tes- ter. It is critical to control both stress and strain in this device. To test the material, you place a sample in a test cell that's constructed in such a way that move- ment of the cell walls creates nearly perfect strain con- ditions at a controlled stress value on the material, as illustrated in Figure 1. The tester applies a load to the material and then moves the cell walls to induce strain at a prescribed stress condition. By measuring the material's particle size distribution before and after applying the stress-strain event, you can characterize the breakage. This process generates data describing the expected increase in the amount of material of a given particle size when exposed to stress-strain conditions of a given magnitude. Figure 2 shows typical data generated for a granular example material with a maximum particle size of 320 microns. The data plotted describes the increase Figure 1 Shear cell for measuring particle breakage potential as a function of strain at a given stress (F = force applied to material during shear) F F F F F Figure 3 Expected increase in minus-160-micron particles when a granular material with a maximum particle size of 320 microns is exposed to stress-strain events 35.00 30.00 25.00 20.00 15.00 10.00 5.00 0.00 Percentage increase Strain (cm/cm) 0 10 20 30 40 50 60 7.5 15.1 23.9 Stress (kilopascals) Figure 2 Expected increase in minus-40-micron particles when a granular material with a maximum particle size of 320 microns is exposed to stress-strain events 35.00 30.00 25.00 20.00 15.00 10.00 5.00 0.00 Percentage increase Strain (cm/cm) 0 10 20 30 40 50 60 7.5 15.1 23.9 Stress (kilopascals)