Enhancing tabletability of high-dose tablets by tailoring properties of spray-dried insulin particles
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Enhancing tabletability of high-dose tablets by tailoring properties of spray-dried insulin particles. / Pedersen, Mahdieh Dagina; Megarry, Andrew; Naelapää, Kaisa; Rades, Thomas; Pessi, Jenni.
In: International Journal of Pharmaceutics, Vol. 631, 122526, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Enhancing tabletability of high-dose tablets by tailoring properties of spray-dried insulin particles
AU - Pedersen, Mahdieh Dagina
AU - Megarry, Andrew
AU - Naelapää, Kaisa
AU - Rades, Thomas
AU - Pessi, Jenni
N1 - Funding Information: The authors wish to thank René Jensen for conducting the ring shear test experiments. Publisher Copyright: © 2022 Elsevier B.V.
PY - 2023
Y1 - 2023
N2 - The oral delivery of proteins and peptides provides an attractive dosing option due to its high patient compliance. However, as oral formulations of such macromolecules require the addition of typically poorly compactable permeation enhancers, the compression behaviour in tableting processes can become challenging. In this study, we show that poor compression behaviour can be overcome by tailoring the properties of peptide or protein particles, especially in high-dose tablet formulations. Spray-dried particles with varying particle size and morphology were produced and characterized. The particles were then evaluated for tabletability in well- and poorly tabletable formulations. Tabletability was found to be enhanced most with small and non-hollow spray-dried insulin particles in both formulations. The enhancement was more pronounced in the poorly tabletable formulation than in the well-tabletable one. Thus, the API particle properties play a key role, when evaluating manufacturability of poorly tabletable formulations.
AB - The oral delivery of proteins and peptides provides an attractive dosing option due to its high patient compliance. However, as oral formulations of such macromolecules require the addition of typically poorly compactable permeation enhancers, the compression behaviour in tableting processes can become challenging. In this study, we show that poor compression behaviour can be overcome by tailoring the properties of peptide or protein particles, especially in high-dose tablet formulations. Spray-dried particles with varying particle size and morphology were produced and characterized. The particles were then evaluated for tabletability in well- and poorly tabletable formulations. Tabletability was found to be enhanced most with small and non-hollow spray-dried insulin particles in both formulations. The enhancement was more pronounced in the poorly tabletable formulation than in the well-tabletable one. Thus, the API particle properties play a key role, when evaluating manufacturability of poorly tabletable formulations.
KW - High-dose formulations
KW - Insulin
KW - Magnesium stearate (CAS: 557-04-0)
KW - Maltitol (CAS: 585-88-6)
KW - MCC (CAS: 9004-34-6)
KW - Oral drug delivery
KW - Oral peptide formulations
KW - Oral protein formulations
KW - Sorbitol (CAS: 50-70-4)
KW - Spray-dried particles
KW - Starch (CAS: 9005-25-8)
KW - Tablet manufacturing
KW - Tabletability
U2 - 10.1016/j.ijpharm.2022.122526
DO - 10.1016/j.ijpharm.2022.122526
M3 - Journal article
C2 - 36565770
AN - SCOPUS:85145333577
VL - 631
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 122526
ER -
ID: 332996291