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ABSTRACT:The compaction behaviour of a commercial granulated clay (magnesium aluminium smectite, gMgSm) was investigated using macroscopic pressure-density measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray microtomography (XµT) and small-angle X-ray scattering (SAXS). This material was studied as a potential compaction excipient for pharmaceutical tabletting, but also as a model system demonstrating the capabilities of SAXS for investigating compaction in other situations.Bulk compaction measurements showed that the gMgSm was more difficult to compact than polymeric pharmaceutical excipients such as spheronised microcrystalline cellulose (sMCC), corresponding to harder granules. Moreover, in spite of using lubrication (magnesium stearate) on the tooling surfaces, rather high ejection forces were observed, which may cause problems during commercial tabletting, requiring further amelioration. Although the compacted gMgSm specimens were more porous, however, they still exhibited acceptable cohesive strengths, comparable to sMCC. Hence, there may be scope for using granular clay as one component of a tabletting formulation.Following principles established in previous work, SAXS revealed information concerning the intragranular structure of the gMgSm and its response to compaction. The results showed that little compression of the intragranular morphology occurred below a relative density of 0·6, suggesting that granule rearrangements or fragmentation were the dominant mechanisms during this stage. By contrast, granule deformation became considerably more important at higher relative density, which also coincided with a significant increase in the cohesive strength of compacted specimens.Spatially-resolved SAXS data was also used to investigate local variations in compaction behaviour within specimens of different shape. The results revealed the expected patterns of density variations within flat-faced cylindrical specimens. Significant variations in density, the magnitude of compressive strain and principal strain direction were also revealed in the vicinity of a debossed feature (a diametral notch) and within biconvex specimens. The variations in compaction around the debossed notch, with a small region of high Clay compaction SAXS -revised PRL 2015-01-03

The pervasiveness of tribo-electric charge during pharmaceutical processing can lead to the exacerbation of a range of problems including segregation, content heterogeneity and particle surface adhesion. The excipients, hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC), are often used in drug delivery systems and so it is important to understand the impact of associated factors on their charging and adhesion mechanisms, however, little work has been reported in this area. Such phenomena become more prominent when excipients are introduced to a powder mixture alongside the active pharmaceutical ingredient(s) (APIs) with inter-and intra-particulate interactions giving rise to electrification and surface adhesion of powder particles. The aim of this study was to understand the impact of material attributes (particle size, hydroxypropoxyl (Hpo) to methoxyl (Meo) ratio and molecular size) on the charging and adhesion characteristics of cellulose ethers. Furthermore, a poorly compactible and highly electrostatically charged drug, flurbiprofen, was used to develop binary powder mixtures having different polymer to drug ratios and the relationship between tribo-electric charging and surface adhesion was studied. Charge was induced on powder particles and measured using a custom built device based on a shaking concept, consisting of a Faraday cup connected to an electrometer. The diversity in physicochemical properties has shown a significant impact on the tribo-electric charging and adhesion behaviour of MC and HPMC.Moreover, the adhesion and electrostatic charge of the API was significantly reduced when MC and HPMC were incorporated and tribo-electric charging showed a linear relationship (R 2 = 0.81-0.98) with particle surface adhesion, however, other factors were also involved. It is anticipated that such a reduction in charge and particle surface adhesion would improve flow and compaction properties during processing.

The use of solid dispersion techniques to modify physicochemical properties and improve solubility and dissolution rate may result in alteration to electrostatic properties of particles. Particle triboelectrification, plays an important part in powder processing, affecting end product quality due to particle deposition and powder loss. This study investigates the use of glucosamine hydrochloride (GLU) in solid dispersions with indomethacin. Solvents selected for the preparation of the dispersions were acetone, acetone-water, ethanol and ethanol-water. Solid state characterizations (DSC, FTIR and XRPD) and dissolution were conducted. Dispersions were subjected to charging using a custom built device based on a shaking concept, consisting of a Faraday cup connected to an electrometer. All dispersions improved the dissolution rate of indomethacin. Analysis showed the method of preparation of the dispersion induced polymorphic forms of the drug. Indomethacin had a high propensity for charging (-411 nC/g). GLU had a very low charge (-1 nC/g). All dispersions had low charges (-1 to 14 nC/g). Acetone as a solvent, or in combination with water, produced samples with an electronegative charge in polarity. The same approach with ethanol produced electropositive charging. The results show the selection of solvents can influence powder charge thereby improving powder handling as well as dissolution properties.