June 5, 2018 PAO-05-18-CL-007
Most active ingredients and adjuvants used in pharma manufacturing are in powder form. Handling and processing of powders is central to pharmaceutical operations, but it poses numerous problems due to their unpredictable and irregular behavior. With recent technological developments, the industry can overcome powder flow hurdles to achieve a quality drug product.1
Powders will behave like both solids and liquids, which leads to product flow issues. As a metaphor, good flow can be compared to granulated sugar, while bad flow can be compared to powdered sugar. Flow issues can result from a product’s reaction to handling issues, such as settling or compaction while in storage, and process equipment issues related to product uniformity, including too much blending—or not enough blending.
A product’s ability to flow is determined by its physical characteristics and its interaction with the processing environment.
Physical characteristics
Bulk densityInteraction with environment
Temperature
Humidity
Hold-time (time spent in storage or containers prior to use)
Often, the result of all powder preparations is not discovered until production, in pharmaceutical applications, that means when the tablets come off the press. While there is no single test method that can adequately characterize powder flow, USP has identified some test methods that may help predict a powder’s likelihood of encountering flow issues in production.2
These include:
Tablet manufacturing processes have a profound effect on how efficient a drug is. As a result of this, the global tablet processing and packaging equipment market is expected to increase from $3,453.0 million in 2017 to 5,268.8 million by 2022. Much of the increased demand for this equipment will, in fact, be for refurbished machines.4
Free-flowing powders are preferred for efficient production and most APIs are not free-flowing powders. The product should flow as fast as the production machine can operate. Certain processing equipment can be used to increase a powder’s mass flow capabilities by changing the product characteristics of the powder. There are various types of processing equipment used to manufacture tablets, such as sieves and mixers, granulators and processors, dryers, mills and blenders.5
There are two main types of sieving–safety screening and grading. Safety screening of powders, sometimes known as control sieving or security/check screening, removes oversized contamination from the powder. Removing the contamination improves the quality of the powder and final product. Grading or sizing of powders or granules separates different ranges of particle sizes to ensure the correct PSD for subsequent tablet pressing.6
Granulation is a common technique to help to improve product flow and achieve mass flow. Powder granulation can reduce inconsistency in particle size, reduce “fines” (very small particles), control dust, and reduce the tendency of powders to segregate. Granulation can be performed wet or dry with high-energy or high-shear mixers; medium energy mixers such as planetary mixers, ribbon blenders, and paddle mixers; or low energy mixers like fluid bed processors, double cone mixers, and twin-shell or “V”-blenders. Another common granulation technique is roller compaction where a roller compactor compresses the powder into strips or tabs to squeeze out air and then the product is milled for consistent particle size.
Many granulators do not have the ability to dry the wet massed granulation, therefore the wet granulation must be moved to the next unit operation, which is called drying. When powders are sensitive to liquids, heat, or both, blend the powders with a pre-granulated dry binder. If the blended powders will not work with the addition of the dry binder and liquid—or heat cannot be used—then dry granulation is used. This method uses mechanical force to densify and compact powders together to form dry granules.
Milling machinery is defined by low-, medium- and high-shear applications. Some milling machines allow for changes in the type of mechanical action used to
reduce the powder to the proper final particle size range. Common milling equipment include: Low-shear mills such as oscillators and comils; medium shear mills, like quick sieves and hammer mills; and high-shear mills, such as pulverizers and blade mills.
Good flow is imperative to attaining a good tablet. Understanding powder characteristics will contribute to accurate blending practices. It’s important to recognize that a “good” final blend is often viewed as such because it has good content uniformity and potency, not by its ability to flow. An individual powder or finished blend may flow very well under one set of circumstance, and not flow well at all under another. The most common blenders used for final blending are the V blender, the double cone blender and the tote blender; all-use low-shear tumble blending as the most effective way to achieve good mixing with a variety of powders and granules.
There are many different variables that can contribute to the success or failure of powder flow on a tablet press. In addition to particle size, shape and distribution, there are also particle surface texture, cohesivity, surface coating, particle interaction, static electricity, recovery from compaction, and wear/attrition while in the holding container. Most powders, without the aid of granulation and flow agents, simply cannot flow at speeds required for high-speed tableting.
Federal Equipment Company offers a diverse range of used equipment meant to improve powder flow, and, through its partnership with Techceuticals, Federal Equipment Company has a wealth of experience in solid-dose manufacturing. This experience includes analyzing the characteristics of many powders, formulations, and equipment needs.
Matt Hicks, Chief Operating Officer at Federal Equipment Company, is a pharmaceutical industry veteran with more than 15 years of experience helping companies get the most value and utility out of their manufacturing and process equipment assets.
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