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powder flow S 18 May 2017 Tablets & Capsules Identifying and controlling segregation in tablet press feed systems Kerry Johanson Material Flow Solutions This article describes the modes of segregation that can occur in tablet press feed systems and how to assess which mode domi- nates. It also provides design strategies to overcome segregation and uses a five-ingredient formulation as an example to illustrate the principles discussed. egregation can be a serious issue when a blend of mul- tiple powders is fed to a tablet press, capsule filler, or other process equipment. This is especially true when the blend contains an API whose ratio must be maintained from the start to the finish of a tablet batch. In such cases, it is important to understand the blend's flow and segregation properties in order to design or select a tablet press feed system that minimizes segregation. Solving a segregation issue from a process standpoint requires understanding four things and summoning the will to make changes. The first step is to measure the seg- regation potential of the blends of interest. When choos- ing the measurement methodology, seek tests that: • Relate to actual processes in the production facility. Many test methods induce a stimulus designed to sepa- rate particles and then assess segregation behavior with- out considering whether the induced stimulus would typ- ically occur in the process. Where possible, use segregation tests that relate to the type of flow behavior you expect during actual production. • Reveal the segregation pattern (i.e., where each ingredient ends up spatially during filling or handling). • Determine the magnitude of segregation ingredient by ingredient. This is typically done and reported as a standard deviation or variance relative to the mean con- centration for each ingredient. In the pharmaceutical industry, this relates to the allowable range for acceptable content uniformity. • Identify and quantify, to the extent possible, the root cause(s) of segregation. Segregation is a mechanistic phe- nomenon with multiple potential causes. Resolving a segre- gation problem requires understanding the specific cause in order to design a feed system that either avoids a stimu- lus that causes particles to separate or optimizes velocity profiles to remix segregated material during handling. Second, review the fill and transfer operations that occur in the actual process after the blending step. The goal here is to identify stimuli that could induce particles to separate and—in conjunction with the segregation test results—compute or estimate the expected segregation pattern that could develop in a vessel after filling or after the blend is transferred. Sometimes the solution is to pre- vent or minimize a stimulus that causes segregation dur- ing filling. Thus, it's critical to understand where the dif- ferent particles end up after filling. Third, understand how flow properties and equipment geometry interact to generate flow profiles in the process. In this step, you must determine the expected velocity profile in the feed system in order to estimate at what point during the emptying cycle each segregating ingredient might leave the system. In many cases, miti- gating segregation requires controlling velocity in the feed devices. Testing may reveal that a blend or ingredi- ent shows moderate segregation, yet by designing the feed system to give the right velocity profiles, it's possible to remix the blend before it reaches the tablet press die. Finally, modify the filling process and/or feed system geometry to eliminate or minimize each cause of segrega- tion and, where the causes cannot be eliminated, design the feed system to create the velocity profiles that can handle the expected segregation pattern. To better understand segregation mitigation, we'll use as an example a drug product blend of 10 percent API and several excipients: microcrystalline cellulose (MCC), lactose, glycolate, and magnesium stearate. Segregation from powder transfers The method used to measure segregation must gener- ate stimuli comparable to those expected in the process that may induce particles to separate from each other. In a typical operation, once the powders are combined in a blender, they enter the feed system above the tablet press or are held in another vessel for later use. In either case,