Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

Research output: Contribution to journalJournal article

Standard

Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient. / Pudasaini, Nawin; Upadhyay, Pratik Pankaj; Parker, Christian Richard; Hagen, Stefan U.; Bond, Andrew; Rantanen, Jukka.

In: Organic Process Research and Development, Vol. 21, No. 4, 2017, p. 571-577.

Research output: Contribution to journalJournal article

Harvard

Pudasaini, N, Upadhyay, PP, Parker, CR, Hagen, SU, Bond, A & Rantanen, J 2017, 'Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient', Organic Process Research and Development, vol. 21, no. 4, pp. 571-577. https://doi.org/10.1021/acs.oprd.6b00434

APA

Pudasaini, N., Upadhyay, P. P., Parker, C. R., Hagen, S. U., Bond, A., & Rantanen, J. (2017). Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient. Organic Process Research and Development, 21(4), 571-577. https://doi.org/10.1021/acs.oprd.6b00434

Vancouver

Pudasaini N, Upadhyay PP, Parker CR, Hagen SU, Bond A, Rantanen J. Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient. Organic Process Research and Development. 2017;21(4):571-577. https://doi.org/10.1021/acs.oprd.6b00434

Author

Pudasaini, Nawin ; Upadhyay, Pratik Pankaj ; Parker, Christian Richard ; Hagen, Stefan U. ; Bond, Andrew ; Rantanen, Jukka. / Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient. In: Organic Process Research and Development. 2017 ; Vol. 21, No. 4. pp. 571-577.

Bibtex

@article{4d654cb1b5f84c519f5bb6f1f1dc78e7,
title = "Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient",
abstract = "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 processability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, 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 (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite was 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.",
author = "Nawin Pudasaini and Upadhyay, {Pratik Pankaj} and Parker, {Christian Richard} and Hagen, {Stefan U.} and Andrew Bond and Jukka Rantanen",
year = "2017",
doi = "10.1021/acs.oprd.6b00434",
language = "English",
volume = "21",
pages = "571--577",
journal = "Organic Process Research and Development",
issn = "1083-6160",
publisher = "American Chemical Society",
number = "4",

}

RIS

TY - JOUR

T1 - Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

AU - Pudasaini, Nawin

AU - Upadhyay, Pratik Pankaj

AU - Parker, Christian Richard

AU - Hagen, Stefan U.

AU - Bond, Andrew

AU - Rantanen, Jukka

PY - 2017

Y1 - 2017

N2 - 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 processability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, 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 (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite was 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.

AB - 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 processability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, 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 (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite was 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.

U2 - 10.1021/acs.oprd.6b00434

DO - 10.1021/acs.oprd.6b00434

M3 - Journal article

VL - 21

SP - 571

EP - 577

JO - Organic Process Research and Development

JF - Organic Process Research and Development

SN - 1083-6160

IS - 4

ER -

ID: 178884045