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Milling induced amorphisation and recrystallization of α-lactose monohydrate

Badal Tejedor, Maria ; Pazesh, Samaneh ; Nordgren, Niklas ; Schuleit, Michael ; Rutland, Mark W. ; Alderborn, Göran and Millqvist-Fureby, Anna LU (2018) In International Journal of Pharmaceutics 537(1-2). p.140-147
Abstract

Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. However, such operations may induce undesired material properties modifications when conditioning particle size through milling, for example. Modification of both surface and bulk material structure will change the material properties, thus affecting the processability of the powder. Hence it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore a surface evaluation of the α-lactose monohydrate after short and prolonged milling times has been... (More)

Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. However, such operations may induce undesired material properties modifications when conditioning particle size through milling, for example. Modification of both surface and bulk material structure will change the material properties, thus affecting the processability of the powder. Hence it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore a surface evaluation of the α-lactose monohydrate after short and prolonged milling times has been performed. Unprocessed α-lactose monohydrate and spray dried lactose were evaluated in parallel to the milled samples as reference examples of the crystalline and amorphous lactose structure. Morphological differences between unprocessed α-lactose, 1 h and 20 h milled lactose and spray dried lactose were detected from SEM and AFM images. Additionally, AFM was used to simultaneously characterize particle surface amorphicity by measuring energy dissipation. Extensive surface amorphicity was detected after 1 h of milling while prolonged milling times showed only a moderate particle surface amorphisation. Bulk material characterization performed with DSC indicated a partial amorphicity for the 1 h milled lactose and a fully amorphous thermal profile for the 20 h milled lactose. The temperature profiles however, were shifted somewhat in the comparison to the amorphous reference, particularly after extended milling, suggesting a different amorphous state compared to the spray-dried material. Water loss during milling was measured with TGA, showing lower water content for the lactose amorphized through milling compared to spray dried amorphous lactose. The combined results suggest a surface-bulk propagation of the amorphicity during milling in combination with a different amorphous structural conformation to that of the amorphous spray dried lactose. The hardened surface may be due to either surface crystallization of lactose or to formation of a low-water glass transition.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Amorphisation, Atomic force microscopy, Differential scanning calorimetry, Lactose, Mechanical properties, Milling, Recrystallization, Tableting, TGA
in
International Journal of Pharmaceutics
volume
537
issue
1-2
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85038844261
  • pmid:29262302
ISSN
0378-5173
DOI
10.1016/j.ijpharm.2017.12.021
language
English
LU publication?
no
additional info
Publisher Copyright: © 2017 Elsevier B.V.
id
72a6693d-efb2-4fee-980f-dffb68ebbf16
date added to LUP
2025-04-02 22:13:20
date last changed
2025-07-10 14:45:50
@article{72a6693d-efb2-4fee-980f-dffb68ebbf16,
  abstract     = {{<p>Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. However, such operations may induce undesired material properties modifications when conditioning particle size through milling, for example. Modification of both surface and bulk material structure will change the material properties, thus affecting the processability of the powder. Hence it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore a surface evaluation of the α-lactose monohydrate after short and prolonged milling times has been performed. Unprocessed α-lactose monohydrate and spray dried lactose were evaluated in parallel to the milled samples as reference examples of the crystalline and amorphous lactose structure. Morphological differences between unprocessed α-lactose, 1 h and 20 h milled lactose and spray dried lactose were detected from SEM and AFM images. Additionally, AFM was used to simultaneously characterize particle surface amorphicity by measuring energy dissipation. Extensive surface amorphicity was detected after 1 h of milling while prolonged milling times showed only a moderate particle surface amorphisation. Bulk material characterization performed with DSC indicated a partial amorphicity for the 1 h milled lactose and a fully amorphous thermal profile for the 20 h milled lactose. The temperature profiles however, were shifted somewhat in the comparison to the amorphous reference, particularly after extended milling, suggesting a different amorphous state compared to the spray-dried material. Water loss during milling was measured with TGA, showing lower water content for the lactose amorphized through milling compared to spray dried amorphous lactose. The combined results suggest a surface-bulk propagation of the amorphicity during milling in combination with a different amorphous structural conformation to that of the amorphous spray dried lactose. The hardened surface may be due to either surface crystallization of lactose or to formation of a low-water glass transition.</p>}},
  author       = {{Badal Tejedor, Maria and Pazesh, Samaneh and Nordgren, Niklas and Schuleit, Michael and Rutland, Mark W. and Alderborn, Göran and Millqvist-Fureby, Anna}},
  issn         = {{0378-5173}},
  keywords     = {{Amorphisation; Atomic force microscopy; Differential scanning calorimetry; Lactose; Mechanical properties; Milling; Recrystallization; Tableting; TGA}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1-2}},
  pages        = {{140--147}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Pharmaceutics}},
  title        = {{Milling induced amorphisation and recrystallization of α-lactose monohydrate}},
  url          = {{http://dx.doi.org/10.1016/j.ijpharm.2017.12.021}},
  doi          = {{10.1016/j.ijpharm.2017.12.021}},
  volume       = {{537}},
  year         = {{2018}},
}