title: Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure.
abstract: 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.
authors.affiliation: SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden; KTH Royal Institute of Technology, Division of Surface and Corrosion Science, Drottning Kristinas väg 51, SE-100 44 Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Badal Tejedor
authors.affiliation: SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Nordgren
authors.affiliation: Novartis Pharma AG, Novartis Institutes for Biomedical Research, GDC, Novartis Campus, 4002 Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Schuleit
authors.affiliation: SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden; KTH Royal Institute of Technology, Division of Surface and Corrosion Science, Drottning Kristinas väg 51, SE-100 44 Stockholm, Sweden.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Rutland
authors.affiliation: SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden. Electronic address: Anna.Fureby@sp.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Millqvist-Fureby
mesh_terms: D000268:Adhesiveness; D002482:Cellulose / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D007785:Lactose / Q000737:chemistry; D008153:Lubrication; D008353:Mannitol / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets / Q000737:chemistry*
chemical_list: D005079:Excipients; D011208:Powders; D013229:Stearic Acids; D013607:Tablets; D008353:Mannitol; C031183:stearic acid; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Adhesion; Atomic force microscopy; Excipients; Profilometry; Surface roughness; Tableting