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b a c k p a g e Reduce powder processing risks when outsourcing manufacturing When outsourcing manufactur- ing for an oral solid dosage product, brand owners generally minimize risk by ensuring that the contract m a n u f a c t u r i n g o r g a n i z a t i o n ' s (CMO's) unit operations have the desired capability and have been tested with the target formulation and that the area has sufficient con- tainment and environmental con- trols. They also typically confirm that the CMO's site leadership team has a demonstrated commitment to quality, analytics, and regulatory compliance. An area of risk that is often overlooked, however, is pow- der transfer between unit operations. Powder transfer has been de- s c r i b e d a s t h e " f o r g o t t e n u n i t operation" in solid dosage manufac- turing, yet it can greatly influence the success of a process. Bulk solids processes have inherent weaknesses at the junctures between unit op- erations. These junctures include chutes, valves, intermediate bulk containers (IBCs), bins, drums, and other methods of moving in-pro- cess powder from point A to point B. The unit operations themselves may work well, but, at full scale, p o wd er m ay n o t reliab ly flo w through these connection points, often resulting in quality defects such as poor content uniformity. The first step in de-risking pow- der transfers is to identify them. Consider where transfers need to take place and how the movements will be controlled. Relying on grav- ity flow is one aspect, as gravity is constant, and an assumption of success often exists as an equipment train is put in place. Unfortunately, grav- ity's effect on powder flow can be highly variable and will depend on the powder's properties. Unlike liq- uid flow, powder flow is influenced by variations in bulk density, wall friction and adhesion to surround- ing surfaces, and cohesive strength within the material, which can all limit a powder's ability to flow by gravity. Liquids can flow through very small openings, but powders often have a minimum outlet size re- quirement to avoid flow obstructions such as cohesive arches and ratholes. Segregation is a separate area of concern and is defined as the separa- tion of a powder into zones of simi- lar properties (which are dissimilar zone to zone). Segregation poten- tial is strongly influenced by particle size differences, but other properties such as particle shape and density can also play a role. Segregation can occur during transfer when forces on the particles are high and the mate- rial is in a dispersed state. Specific mechanisms include sifting, where interparticle motion occurs as a pile forms, and fluidization and dusting, which can occur due to air exchange as an open volume is rapidly filled in with free falling powder from above. System components that are in- tended to control powder flow can be an additional source of concern. Feeders can contribute to flow be- haviors where some portions of the connection above are stagnant, with areas of non-flowing powder within them when the system is running, making them more likely to experi- ence a flow obstruction even when the inlet area is relatively large. Pinch valves and gates that do not fully open are further risk factors, as they inherently contribute to stagna- tion by restricting a portion of their throat area. You don't need to wait for a problem to arise to reduce the risks associated with powder trans- fer steps. Developing a basic suite of flow properties for the powders being handled at each stage allows for a technical evaluation of transfer steps. The goal of this effort is to develop a set of engineering param- eters that you can use to evaluate a CMO's actual production process. The most important properties in- clude cohesive strength, to deter- mine the minimum opening sizes a powder will pass through without arching or ratholing; wall friction, to determine hopper and/or chute angle requirements as a function of surface material of construction and finish; permeability, to determine critical opening sizes for steady flow rates; and segregation potential by sifting and fluidization, to consider the influence of forces during trans- fer that could give rise to content uniformity variations. If you know your material's flow properties, you can quantitatively assess the powder flow performance of your CMO's handling system, allowing you to solve or avoid problems at the outset based on equipment features. T&C Roger A. Barnum (rbarnum@jenike. com) is a director with Jenike & Johan- son, Tyngsboro, MA ( 9 7 8 6 4 9 3 3 0 0 , The company provides bulk material testing and other services related to bulk solids flow and segregation pre- vention to the pharmaceutical, chemical, foods, mining, and other industries.

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