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The present study used a range of particle sizes, from 2 to 100 μm, and tested three carrier-based formulations and their corresponding carrier-free systems with a range of drug-to-carrier ratios. The carrier-based powders were manufactured by a spray-drying process and were of a type typically encountered in commercial formulations. The spray-drying process was successful and was shown to yield particles with good flow properties and compactibility. The carrier-based powders showed low-to-intermediate flow rates and a range of bulk densities (0.3-2.0 g/cm3) that are typical of commercial powders. The carrier-free systems showed excellent flowability and bulk density. Powder flow rates through the USP throat indicated that the carrier-based systems show moderate to high flow resistance and the particle-size-based density distribution showed that the bulk densities of the carrier-free systems are independent of the particle size. The carrier-free systems had a more pronounced peak of the particle-size-based density distribution at the lower end of the specified particle size range, which is expected for carrier-free systems with high flowability. This trend is in accordance with expectations based on the particle size-dependent flow rate. The carrier-based systems showed significantly higher flow rates through the USP throat than the carrier-free systems at the same carrier-drug ratio, demonstrating that the carrier-based systems are more resistant to flow-induced de-agglomeration.
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