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Milling induced amorphisation andrecrystallization of α-lactose monohydrate
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science. RISE Research Intitutes of Sweden.ORCID iD: 0000-0001-5894-7123
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2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 537, no 1-2, p. 140-147Article in journal (Refereed) Published
Abstract [en]

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 alpha-lactose monohydrate after short and prolonged milling times has been performed. Unprocessed alpha-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 un-processed a-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 spraydried 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.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 537, no 1-2, p. 140-147
Keyword [en]
tableting, milling, lactose, amorphisation, recrystallization, mechanical properties, atomic force microscopy, differential scanning calorimetry, TGA
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:kth:diva-220332DOI: 10.1016/j.ijpharm.2017.12.021ISI: 000424263700016PubMedID: 29262302Scopus ID: 2-s2.0-85038844261OAI: oai:DiVA.org:kth-220332DiVA, id: diva2:1167352
Note

QC 20171219

Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2018-02-22Bibliographically approved
In thesis
1. Interfacial and material aspects of powders with relevance to pharmaceutical tableting performance
Open this publication in new window or tab >>Interfacial and material aspects of powders with relevance to pharmaceutical tableting performance
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tablets are the most common forms of drug administration. They are convenient to administer and easy to manufacture. However, problems associated with the adhesion of the powders to the tableting tools are common. This phenomenon is known as sticking and even though it has been well documented and studied, it remains poorly understood. The many factors that contribute to good performance of the powders make the sticking problem difficult to solve.

The goal of this study is to establish a relationship between the properties measured at the nanoscale to the overall tablet mechanical properties, tablet performance and powder pre-processing induced modifications. By using atomic force microscopy (AFM) we aim to develop an analytical method to characterize the mechanical and adhesive properties of the pharmaceutical powders at the nanoscale. Other methodologies such as scanning electron microscopy (SEM), thermal analyses (DSC, TGA) and tablet strength test were also used. The materials used in this study are commonly used excipients, a sticky drug and magnesium stearate (MgSt). Two different approaches offered by AFM were employed: sharp tip imaging and colloidal probe force measurements. Nano-mechanical properties of the materials were evaluated with a sharp tip cantilever showing that higher adhesion correlates with higher tablet cohesion and that both are significantly affected by the presence of MgSt. AFM characterization of the particle surface mechanical properties at the nanoscale was also used to detect the crystallinity and amorphicity levels of the materials. New approaches to presenting such data considering the particle heterogeneity and to track the dynamics of surface recrystallization are revealed. Adhesive interactions between a steel sphere and sticky and non-sticky powders were performed with the colloidal probe technique. Sticky materials presented a higher adhesion against the steel surface, and reveal the mechanism of stickiness.

This work thus contributes to the provision of predictability of the performance of formulations at an early stage of the development process.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. p. 92
Series
TRITA-CHE-Report, ISSN 1654-1081 ; 2017:14
Keyword
atomic force microscopy, excipients, surface characterization, tableting, milling, amorphisation
National Category
Materials Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:kth:diva-203125 (URN)978-91-7729-293-7 (ISBN)
Public defence
2017-03-24, F3, Stockholm, 10:00 (English)
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Supervisors
Note

QC 20170315

Available from: 2017-03-15 Created: 2017-03-13 Last updated: 2017-12-18Bibliographically approved

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Badal Tejedor, MariaRutland, Mark W.

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