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Bateman, SD
Languages: English
Types: Doctoral thesis
Subjects: RM

Classified by OpenAIRE into

mesheuropmc: organic chemicals
A high speed hydraulic press has been developed into a computer controlled high speed compression Simulator, capable of reproducing displacement time profiles seen on any production tabletting machine. The system has been validated to monitor punch displacements to ?12pm and loads to ?O.05% of full scale. Confidence in the results obtained using the Simulator were enhanced by comparison with other operational Simulators. The established Simulator was then used to investigate the\ud effects of compression on ibuprofen. Ibuprofen was found to consolidate mainly by plastic deformation with a lesser contribution from the melting of asperities. A significant amount of pressure induced melting and subsequent fusion bonding occurred at higher pressures. Ibuprofen was found to be sensitive to the magnitude and rate of application of the compression pressure. The extent of plastic flow exhibited by ibuprofen during compression was, found to decrease as the compression speed increased. Lamination and capping of ibuprofen compacts at high compression speeds was considered to be due to a combination of air entrapment and the inability of the compact to withstand the stresses of decompression.\ud When ibuprofen was mixed with a second material and compressed, the consolidation mechanism and properties of the compacts formed were found to follow complex relationships. The relationships were dependant on the proportion of each material and the speed of compression. For ibuprofen microcrystalline cellulose mixtures positive interactions were considered to occur due to bonding between the two materials. For ibuprofen and lactose mixtures the interactions observed were considered to be a balance between the plastic deformation by the ibuprofen relieving the applied load preventing the cri tical force required for fracture of the lactose being attained, and the lactose fragments bearing the applied load reducing plastic flow by ibuprofen. The Simulator was then employed to investigate different aspects of tabletting machine design. A simple ibuprofen microcrystalline cellulose mixture and a commercial ibuprofen formulation were compressed to a constant load and then to a constant thickness and the properties of the compacts compared. Tablets prepared under a constant maximum applied load, with fill weights varied over the B.P uniformity of weight limits, had relatively constant disintegration times and radial tensile strengths. This was considered an advantage over the tablets prepared to a constant thickness which showed considerable varia?tion under the same conditions. The second aspect of tabletting machine design to be investigated was the use of relatively high precompression pressures using a commercially available paracetamol granulation. The maximum compression pressure exerted during the tableting cycle was found to be the major factor contributing to the tensile strength of the tablets. The use of a second compression either before or after the main compression was found to produce a significant increase in tablet tensile strength. The greater the magnitude of the second compression, the greater its effect on tensile strength. The contribution of a second compression towards the tablet tensile strength was attributed to the effective increase in dwell time it generated. The orientation of the greater and lesser compression pressures during tableting was found to influence the tablet tensile strength. Stronger tablets resulted if the greater pressure was exerted first. This was considered to be a function of temperature increases within the tablet and the disruptive effects of the second compression.
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