α-Lactose monohydrate – new insights into physicochemical response to temperature and humidity exposure
(2026) In International Journal of Pharmaceutics 694.- Abstract
Environmental relative humidity (RH) and temperature (T) are known to be promoters of physicochemical changes in pharmaceutical grade lactose, either in controlled (supervised conditioning), or uncontrolled (during transit and repository storage) scenarios. Comprehensive knowledge of this excipient's material characteristics prior to its use in formulation development is therefore a fundamental requirement. In this work, two kinetic processes are identified and characterized, namely crystallization and relaxation. The former is driven mainly by recrystallization of amorphous surface regions and may lead to particle aggregation and apparent growth, while the latter is explained by long-term structural reorganization and smoothing of... (More)
Environmental relative humidity (RH) and temperature (T) are known to be promoters of physicochemical changes in pharmaceutical grade lactose, either in controlled (supervised conditioning), or uncontrolled (during transit and repository storage) scenarios. Comprehensive knowledge of this excipient's material characteristics prior to its use in formulation development is therefore a fundamental requirement. In this work, two kinetic processes are identified and characterized, namely crystallization and relaxation. The former is driven mainly by recrystallization of amorphous surface regions and may lead to particle aggregation and apparent growth, while the latter is explained by long-term structural reorganization and smoothing of particle surfaces. By quantitatively determining changes in amorphicity, particle size distribution, specific surface area, crystal structure and thermal properties, a two-step fitting kinetic model is proposed which captures experimental trends. The results show that while the crystallization component and initial relaxation is mainly driven by relative humidity, the long-term relaxation, which has a continuous impact on specific surface area, is less dependent on temperature and humidity and is only partially related to changes in amorphicity and apparent particle size.
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- author
- Sanchez-Valencia, Andrea LU ; Husman-Piirainen, Johanna ; Kokkonen, Päivi ; Merikivi, Annika ; Toppari, Antti ; Thalberg, Kyrre LU ; van Veen, Bert and Briggner, Lars Erik
- organization
- publishing date
- 2026-04-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amorphicity, Crystallization, Lactose, Particle size, Physicochemical properties, Relaxation, Specific surface area
- in
- International Journal of Pharmaceutics
- volume
- 694
- article number
- 126710
- publisher
- Elsevier
- external identifiers
-
- pmid:41794350
- scopus:105033131038
- ISSN
- 0378-5173
- DOI
- 10.1016/j.ijpharm.2026.126710
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2026
- id
- b5d01e4a-49b7-451b-9c1c-e34bedb66013
- date added to LUP
- 2026-04-27 14:00:44
- date last changed
- 2026-09-02 05:51:10
@article{b5d01e4a-49b7-451b-9c1c-e34bedb66013,
abstract = {{<p>Environmental relative humidity (RH) and temperature (T) are known to be promoters of physicochemical changes in pharmaceutical grade lactose, either in controlled (supervised conditioning), or uncontrolled (during transit and repository storage) scenarios. Comprehensive knowledge of this excipient's material characteristics prior to its use in formulation development is therefore a fundamental requirement. In this work, two kinetic processes are identified and characterized, namely crystallization and relaxation. The former is driven mainly by recrystallization of amorphous surface regions and may lead to particle aggregation and apparent growth, while the latter is explained by long-term structural reorganization and smoothing of particle surfaces. By quantitatively determining changes in amorphicity, particle size distribution, specific surface area, crystal structure and thermal properties, a two-step fitting kinetic model is proposed which captures experimental trends. The results show that while the crystallization component and initial relaxation is mainly driven by relative humidity, the long-term relaxation, which has a continuous impact on specific surface area, is less dependent on temperature and humidity and is only partially related to changes in amorphicity and apparent particle size.</p>}},
author = {{Sanchez-Valencia, Andrea and Husman-Piirainen, Johanna and Kokkonen, Päivi and Merikivi, Annika and Toppari, Antti and Thalberg, Kyrre and van Veen, Bert and Briggner, Lars Erik}},
issn = {{0378-5173}},
keywords = {{Amorphicity; Crystallization; Lactose; Particle size; Physicochemical properties; Relaxation; Specific surface area}},
language = {{eng}},
month = {{04}},
publisher = {{Elsevier}},
series = {{International Journal of Pharmaceutics}},
title = {{α-Lactose monohydrate – new insights into physicochemical response to temperature and humidity exposure}},
url = {{http://dx.doi.org/10.1016/j.ijpharm.2026.126710}},
doi = {{10.1016/j.ijpharm.2026.126710}},
volume = {{694}},
year = {{2026}},
}