Solid state characterisation and compaction behaviour of pharmaceutical materials

Abstract: In this thesis, factors important in tableting operations and for tablet properties have been studied and characterised by different spectroscopic techniques as well as by some more conventionally used particle characterisation techniques. The spectroscopic techniques solid-state NMR, FT-IR and NIR spectroscopy, proved to be valuable tools in the estimation of particle and tablet properties, offering both specificity and sensitivity in the measurements. Because of the large amount of information obtained in a spectrum, multivariate data analysis was in some cases used in the processing of the spectral data. Correlations between the solid state structure measured by spectroscopy and the particle and tablet properties could be obtained including useful prediction models.The surface area obtained using different principles has in this thesis been shown to reflect different properties and tableting behaviour of a collection of pharmaceutical materials. The particle shape and the external surface area of the powders measured by permeametry, were found to be important factors for the tensile strength of tablets made of hydroxypropyl methylcellulose. Furthermore, the external surface area could be used to access dominating interparticulate bonding mechanisms in compacts of different materials by normalising the tablet tensile strength for the tablet surface area. It was also shown that for materials prone to develop solid bridges, the actual surface area participating in the bonding was more important than the average interparticulate distance. When studying the properties of microcrystalline cellulose and cellulose powder from the alga Cladophora sp., the cellulose fibril surface area estimated by solid-state NMR resulted in better correlations to the tableting behaviour and to tablet disintegration than the external permeametric surface area did. It was suggested that the difference in fibril surface area of the two celluloses was the primary factor responsible for properties like the crystallinity and the disintegration of the tablets.