Varied Bulk Powder Properties of Micro-Sized API within Size Specifications as a Result of Particle Engineering Methods
Micronized particles are commonly used to improve the content uniformity (CU), dissolution performance, and bioavailability of active pharmaceutical ingredients (API). Different particle engineering routes have been developed to prepare micron-sized API in a specific size range to deliver desirable biopharmaceutical performance. However, such API particles still risk varying bulk powder properties critical to successful manufacturing of quality drug products due to different particle shapes, size distribution, and surface energetics, arising from the anisotropy of API crystals. In this work, we systematically investigated key bulk properties of 10 different batches of Odanacatib prepared through either jet milling or fast precipitation, all of which meet the particle size specification established to ensure equivalent biopharmaceutical performance. However, they exhibited significantly different powder properties, solid-state properties, dissolution, and tablet CU. Among the 10 batches, a directly precipitated sample exhibited overall best performance, considering tabletability, dissolution, and CU. This work highlights the measurable impact of processing route on API properties and the importance of selecting a suitable processing route for preparing fine particles with optimal properties and performance.
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Various lots of Odanacatib were obtained from Merck & Co., Inc. (Rahway, NJ, USA). Ethanol (200 proof) was purchased from Decon Labs, Inc. (King of Prussia, PA, USA). DMF and acetone were used to prepare precipitated samples and were purchased from Fisher Scientific (Fair Lawn, NJ, USA). Pharmaceutical excipients used in this work, i.e., Avicel PH102 (MCC; FMC Biopolymers; Newark, DE, USA), spray-dried lactose monohydrate (LM; Foremost; Baraboo, WI, USA), Kollidon VA64 (Crospovidone; BASF; Ludwigshafen, Germany), sodium stearyl fumarate (SSF; JRS Pharma; Patterson, NY, USA) magnesium stearate (MgSt; Covidien, Dublin, Ireland) were used as received.
Wang, Z.; Solomos, M.; Axnanda, S.; Chen, C.; Figus, M.; Schenck, L.; Sun, C.C. Varied Bulk Powder Properties of Micro-Sized API within Size Specifications as a Result of Particle Engineering Methods. Pharmaceutics 2022, 14, 1901. https://doi.org/10.3390/pharmaceutics14091901