title: Multivariate analysis of relationships between material properties, process parameters and tablet tensile strength for alpha-lactose monohydrates.
abstract: The present work describes an approach to quantify relationships between the material properties of various alpha-lactose monohydrate grades (alphaLM), process parameters (punch velocity, lubricant fraction) and the tablet tensile strength (TS). Milled, sieved, agglomerated and spray-dried alphaLMs were studied. Each material was tableted (11 mm flat punches, constant true volume of 0.2833 cm(3)) on a compaction simulator at a pressure of 104.4+/-0.1 MPa. The force-displacement data was analyzed by applying a combination of compression descriptors (derived from Kawakita and Heckel equations, work-related parameters). The relationships were evaluated and quantified by principal component analysis (PCA) and partial least square regression (PLS-1). PCA verified fundamental relationships between different powder and compression properties of studied materials. It was found that the compression descriptors Kawakita '1/b' and WoC were sufficient to distinguish the tested alphaLM-grades, even in combination with different lubricant fraction or by utilizing different punch velocities; the identified descriptors correlated with TS. These relationships were quantified by PLS-1. Finally, TS were successfully predicted for all alphaLM with the help of separate optimized PLS-1 models. The present study shows an approach how to extract relevant information about tableting behavior from a limited amount of material.
authors.affiliation: University of Tromsø, Department of Pharmacy, Tromsø, Norway.
authors.forename: Rahul V
authors.initials: RV
authors.lastname: Haware
authors.forename: Ingunn
authors.initials: I
authors.lastname: Tho
authors.forename: Annette
authors.initials: A
authors.lastname: Bauer-Brandl
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D016018:Least-Squares Analysis; D054327:Lubricants / Q000737:chemistry; D015999:Multivariate Analysis; D011208:Powders; D025341:Principal Component Analysis; D013607:Tablets; D013718:Tensile Strength
chemical_list: D005079:Excipients; D054327:Lubricants; D011208:Powders; D013607:Tablets; D007785:Lactose