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Investigation of the effects of particle size on fragmentation during tableting.
Int J Pharm. 2020 Feb 25; 576:118985.IJ

Abstract

Particle size is a critical parameter during tablet production as it can impact tabletability, flowability, and dissolution rate of the final product. The purpose of this study was to investigate the effect of initial particle size on fragmentation of pharmaceutical materials during tableting. Initial particle size fractions ranging from 0-125 to 355-500 µm of dibasic calcium phosphate (DCP), lactose monohydrate, and agglomerated and non-agglomerated microcrystalline cellulose (MCC) were blended with magnesium stearate and compressed into tablets. Larger initial particle sizes were found to fragment more extensively than smaller initial particle sizes for all materials based on the particle size distributions determined by laser diffraction. DCP was found to fragment most extensively followed by lactose and both MCCs. The fragmentation degrees of DCP, lactose, agglomerated and non-agglomerated MCC reached 95, 81, 32, and 29%, respectively. These findings were further supported by an increase in specific surface area with increasing compression pressure of compressed particles. The NIR spectral baseline offset from tablets was found to increase with increasing compression pressure up to 50 MPa for all materials, which was the same compression pressure range where fragmentation was observed. The NIR spectral slope from tablets as a function of compression pressure furthermore showed a similar trend as the tabletability profiles. NIR spectroscopy can thereby potentially be used as a surrogate control strategy for assessing compression related particle size changes and possibly tablet density and deformation behavior during tablet production.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Skelbæk-Pedersen AL
Oral Pilot & Process Development Department, Novo Nordisk A/S, Måløv, Denmark; Department of Pharmacy, University of Copenhagen, Denmark. Electronic address: apse@novonordisk.com.
Vilhelmsen TK
Oral Pilot & Process Development Department, Novo Nordisk A/S, Måløv, Denmark.
Wallaert V
Oral Pilot & Process Development Department, Novo Nordisk A/S, Måløv, Denmark.
Rantanen J
Department of Pharmacy, University of Copenhagen, Denmark.

MeSH

Calcium PhosphatesCelluloseChemistry, PharmaceuticalExcipientsLactoseParticle SizePressureStearic AcidsTabletsTechnology, PharmaceuticalTensile Strength

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31870957

Citation

Skelbæk-Pedersen, Anne Linnet, et al. "Investigation of the Effects of Particle Size On Fragmentation During Tableting." International Journal of Pharmaceutics, vol. 576, 2020, p. 118985.
Skelbæk-Pedersen AL, Vilhelmsen TK, Wallaert V, et al. Investigation of the effects of particle size on fragmentation during tableting. Int J Pharm. 2020;576:118985.
Skelbæk-Pedersen, A. L., Vilhelmsen, T. K., Wallaert, V., & Rantanen, J. (2020). Investigation of the effects of particle size on fragmentation during tableting. International Journal of Pharmaceutics, 576, 118985. https://doi.org/10.1016/j.ijpharm.2019.118985
Skelbæk-Pedersen AL, et al. Investigation of the Effects of Particle Size On Fragmentation During Tableting. Int J Pharm. 2020 Feb 25;576:118985. PubMed PMID: 31870957.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of the effects of particle size on fragmentation during tableting. AU - Skelbæk-Pedersen,Anne Linnet, AU - Vilhelmsen,Thomas Kvistgaard, AU - Wallaert,Vibeke, AU - Rantanen,Jukka, Y1 - 2019/12/21/ PY - 2019/10/07/received PY - 2019/12/10/revised PY - 2019/12/19/accepted PY - 2019/12/25/pubmed PY - 2020/11/18/medline PY - 2019/12/25/entrez KW - Compression KW - Deformation KW - Fragmentation KW - Near-infrared KW - Particle size KW - Process monitoring KW - Tableting SP - 118985 EP - 118985 JF - International journal of pharmaceutics JO - Int J Pharm VL - 576 N2 - Particle size is a critical parameter during tablet production as it can impact tabletability, flowability, and dissolution rate of the final product. The purpose of this study was to investigate the effect of initial particle size on fragmentation of pharmaceutical materials during tableting. Initial particle size fractions ranging from 0-125 to 355-500 µm of dibasic calcium phosphate (DCP), lactose monohydrate, and agglomerated and non-agglomerated microcrystalline cellulose (MCC) were blended with magnesium stearate and compressed into tablets. Larger initial particle sizes were found to fragment more extensively than smaller initial particle sizes for all materials based on the particle size distributions determined by laser diffraction. DCP was found to fragment most extensively followed by lactose and both MCCs. The fragmentation degrees of DCP, lactose, agglomerated and non-agglomerated MCC reached 95, 81, 32, and 29%, respectively. These findings were further supported by an increase in specific surface area with increasing compression pressure of compressed particles. The NIR spectral baseline offset from tablets was found to increase with increasing compression pressure up to 50 MPa for all materials, which was the same compression pressure range where fragmentation was observed. The NIR spectral slope from tablets as a function of compression pressure furthermore showed a similar trend as the tabletability profiles. NIR spectroscopy can thereby potentially be used as a surrogate control strategy for assessing compression related particle size changes and possibly tablet density and deformation behavior during tablet production. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/31870957/Investigation_of_the_effects_of_particle_size_on_fragmentation_during_tableting_ DB - PRIME DP - Unbound Medicine ER -