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26 July 2020 Tablets & Capsules though it is more abrasive on tablet tooling than MCC. Often, formulators will use a mixture of these two com- pounds for the diluent, which will make up the bulk of the formulation. Sodium starch glycolate is often used as a disintegrant in DC tableting due to its ability to absorb water and expand. This disintegration property enhances the disin- tegration effect of MCC. Magnesium stearate is used as a lubricant in DC tablet- ing because it tends to reduce friction and adhesion between the formulation and the tablet tooling during compression. However, excess magnesium stearate can hinder the resulting tablet's dissolution by forming a hydrophobic layer around the particles in the formulation. The API is often one of the finest components in a formulation and is usually cohesive. In general, adding cohesion to a material that is prone to segregate will tend to reduce the segregation, but it may also change the seg- regation mechanism. Segregation is also a function of the concentration of key components. Figure 2 shows the measured pile segregation profile for a formulation containing these ingredients with an API concentration of 2 percent. The segregation profile is plotted as a function of the dimensionless radius, with 0.0 representing the top of the pile and 1.0 representing the bottom of the pile. The MCC and lactose are mixed in a 1:1 ratio and, as the figure shows, their segregation pat- terns seem to be opposite from one another. When the within the US content uniformity range for many phar- maceuticals. Therefore, if all of a formulation's important measured segregation intensity numbers are lower than 3.3 percent, the risk of segregation is very low, and that formulation could be put into almost any process and generate a uniform product. If the segregation test gives a segregation inten- sity number low enough, then no additional analysis is required. However, for formulations with segregation intensity numbers above 3.3 percent, before you can mit- igate the segregation you will also need to know the seg- regation pattern as well as the mechanism. Analysis of an example formulation There are two ways to solve a segregation problem: The formulator can design the material so that it does not segregate, or the engineer can design the process so that the material is not segregated either in time or spatial dimension when it discharges from the process. Consider a typical direct-compression (DC) tablet blend consisting of microcrystalline cellulose (MCC), lactose, sodium starch glycolate, magnesium stearate, and an API. Formulators often use MCC as a binder and dilu- ent in DC tableting; it tends to have some disintegration properties and is relatively easy on tablet tooling due to its lubrication and compressibility properties. Lactose is also a diluent and is widely used in DC tableting because of its good binding and compression characteristics, Figure 2 Segregation profile of example drug formulation (2 percent API concentration) 100 90 80 70 60 50 40 30 20 10 0 Concentration (%) 0.0 0.2 0.4 0.6 0.8 1.0 r Rt MCC Lactose Glyco Lubricant API MCC + lactose Dimensionless radius (r/Rt) Segregation intensity (%) MCC 10.23 Lactose 10.15 Glyco 26.17 Lubricant 35.23 API 29.83 MCC + lactose 0.22