TY - JOUR
T1 - Varied Bulk Powder Properties of Micro-Sized API within Size Specifications as a Result of Particle Engineering Methods
AU - Wang, Zijian
AU - Solomos, Marina
AU - Axnanda, Stephanus
AU - Chen, Chienhung
AU - Figus, Margaret
AU - Schenck, Luke
AU - Sun, Changquan Calvin
N1 - Funding Information:
This research was supported by a grant from Merck.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - bulk properties
KW - contact angle
KW - particle engineering
KW - particle size
KW - surface anisotropy
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U2 - 10.3390/pharmaceutics14091901
DO - 10.3390/pharmaceutics14091901
M3 - Article
C2 - 36145649
AN - SCOPUS:85138596049
SN - 1999-4923
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 9
M1 - 1901
ER -
