Issue link: https://www.e-digitaleditions.com/i/819216
Figure 4 Concentration of API due to formation of a pile Concentration Dimensionless radius (r/Ht) 0 0.2 0.4 0.6 0.8 1 14% 12% 10% 8% 6% 4% 2% 0% Glycolate Mag stearate API Rt r Material Segregation intensity (relative to mean) MCC MCC - Lactose Mag stearate 28.49% Glycolate 16.37% API 1.30% 24.76% 3.70% 2.57% Lactose 20 May 2017 Tablets & Capsules Figure 3 Concentration of key components due to formation of a pile 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Concentration Dimensionless radius (r/Ht) 0 0.2 0.4 0.6 0.8 1 r Rt Material Segregation intensity (relative to mean) MCC MCC - Lactose Mag stearate 28.49% Glycolate 16.37% API MCC - Lactose Lactose Mag stearate Glycolate API MCC 1.30% 24.76% 3.70% 2.57% Lactose events. Next, the concentrations of the blend's five ingre- dients were determined using a spectroscopic segregation tester [1]. This automated tester measured 25 samples along the depth of the column. Because segregation due to fluidization events often occurs near the boundaries of the material, the data were biased to take more measurements at the top and bottom. Figure 2 shows the results. The data in figures 1 and 2 are presented as a dimen- sionless depth (h/Ht), where (h) is the distance from the top of the material and (Ht) is the depth at the bottom of the column. Point 0.0 represents material at the top of the column and 1.0 represents material at the bottom. The API shows only a minor segregation tendency but has three distinct increases in concentration at various column depths. These higher concentrations could have been caused by the three fluidization events. The glyco- late shows major fluidization segregation, concentrating at the top of the column, and there appears to be inter- play between the glycolate and two other excipients, MCC and lactose. This shows the importance of measur- ing the segregation profile of all ingredients in the blend. API segregation is within an acceptable range, but the other ingredients segregate relative to each other. This is a common occurrence when there are more than two ingredients. Most current literature—and less stringent segregation test protocols—deal with segregation in bimodal systems and pinpoint only one cause. Although it is possible to find measurements of simple bimodal materials, they offer little help in understanding the com- plexity of segregation in real blends. To be worthwhile, the test protocol should measure segregation in multi- ingredient blends after subjecting the material to a stimu- lus that is process-specific. From this single segregation test, we learned that the API will not likely separate significantly when the blend is trans- ferred to a receiving vessel. However, if the blend cannot be remixed before it gets to the die filling station, the amount of glycolate (a glidant) in each tablet may vary, and there may be flow problems during the tabletting run.