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As for segregation, it typically is influenced by whether the blend is ordered (interactive) or random. Segregation is rare in ordered blends because there is a high amount of interaction between the API and excipi- ent particles. The opposite is true of random blends, where the low level of interaction between the API and excipient particles frequently leads to greater segregation (Figure 4). Study Levothyroxine is an API known to segregate in low- dose formulations. It was chosen as a model API for sev- eral experiments in which two different grades of MCCs were tested to determine which material would limit seg- regation better in low-dose formulations of levothyrox- ine. Highly water soluble APIs typically show a low tri- boelectric charge because of their hydrophilicity. These low-charge materials are likely to have less interaction with the excipients and thus are more likely to result in a random blend that has a high potential to segregate. Figure 5 shows the results of tests conducted on multiple APIs to assess their triboelectric charge. The tests of levothyroxine gave a result of 1.1 nanocoloumbs per gram (nC/g). The model formulation used in this experiment con- tained levothyroxine (0.1 percent), MCC (80 percent), crosscarmellose sodium (2 percent), D-mannitol (16.9 percent), and magnesium stearate (1 percent). To assess the anti-segregation effect, the novel MCC was com- pared with the industry standard MCC, PH-102. The process mixed the levothyroxine, MCC, croscarmellose, and mannitol in a V-type blender for 117 minutes. Then the magnesium stearate was added and the powders were blended for an additional 3 minutes. During blending, the samples were taken every 30 min- utes to determine the effect of the process on blend uni- formity. At the end of the process, the blend was dis- charged and compressed into tablets on a rotary press. Tablets & Capsules July 2017 25 Figure 2 Micrograph of the novel MCC's particles [1] Figure 3 Micrograph of cross-section of the novel MCC's particle [1] Table 1 Properties of different MCC grades Bulk density (g/cm 3 ) Average particle size (microns) Repose angle (degrees) Oil- absorbing capacity (%) KG-1000 0.12 50 57 270 KG-802 0.21 50 49 200 PH-101 0.29 50 45 190 PH-102 0.30 90 42 180 PH-200 0.35 180 36 150 PH-301 0.41 50 41 120 PH-302 0.42 90 38 200 Novel MCC [1] 0.29 100 34 190 Figure 4 Characteristics of ordered and random mixtures Ordered (interactive) mixture Segregation rarely occurs. API particles are steadily supported on excipient particles due to high interaction between API and excipient. Random mixture Segregation occurs frequently. Low interaction between API and excipient causes segregation because API and excipent particles move independently. Current technique Trituration Composite particle Wet granulation Excipient API Figure 5 Triboelectric charge of various APIs Charge quantity (nC/g) Charged condition Static condition Ethenzamide MCPA Ascorbic acid Sodium salicylate Aspirin Ibuprofen Acetaminophen 20 15 10 5 0 Interaction between API and excipient = adhesion force of API Low High 3.0 kV x200 100μm 0000 05/OCT 07