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Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.ORCID iD: 0000-0002-8935-8070
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2015 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 486, no 1-2, 315-323 p.Article in journal (Refereed) Published
Abstract [en]

Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture.

Place, publisher, year, edition, pages
2015. Vol. 486, no 1-2, 315-323 p.
Keyword [en]
Adhesion, Atomic force microscopy, Excipients, Profilometry, Surface roughness, Tableting, lactose, magnesium stearate, mannitol, microcrystalline cellulose, Article, chemical binding, chemical structure, controlled study, drug formulation, elasticity, hydrophilicity, lubrication, mechanics, priority journal, scanning electron microscopy, strength, tablet, tablet hardness, tablet property, tablet surface
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-167709DOI: 10.1016/j.ijpharm.2015.03.049ISI: 000353999100034Scopus ID: 2-s2.0-84928336238OAI: oai:DiVA.org:kth-167709DiVA: diva2:815902
Note

QC 20150602

Available from: 2015-06-02 Created: 2015-05-22 Last updated: 2017-12-04Bibliographically 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. 92 p.
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)
Opponent
Supervisors
Note

QC 20170315

Available from: 2017-03-15 Created: 2017-03-13 Last updated: 2017-03-16Bibliographically approved

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