Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

作者：Pudasaini Nawin; Upadhyay Pratik P; Parker Christian R; Hagen Stefan U; Bond Andrew D; Rantanen Jukka^*

来源：Organic Process Research & Development, 2017, 21(4): 571-577.

DOI：10.1021/acs.oprd.6b00434

Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA): This study reports procesability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombphedrals, elongated hexagons, and spheroids) in the context of direct compression using ring shear-tester, flow rate analyzer, and instrumented tablet press. As expected, needles were very cohesive, had low flow rate (1.0 +/- 0:08 mg/s), and low bulk density (0.141 +/- 0.01 g/mL)but showed better tabletability,whereas the opposite We observed with more isotropic crystal habits. For instance, spheroids, elongated hexagons, and rhombohedrals were easy/free-flowing and had high bulk densities (>= 0.5 g/mL), but final tablets had lower tensile strength than that of needles. Of the six crystal habits, the plates showed a good compromise considering both flowability and tabletability.

• 出版日期2017-4