Role of Mechanical Stress, Excipients and Coprocessing On Tablet Mechanical Properties

The general objective of this work was to understand the role of compression speed and powder co-processing on tablet mechanical properties. In the first chapter, the effect of compression speed on compressibility, tabletability, and compactibility profiles of various materials was explored. The advantage of utilizing a compactibility profile in reducing the effect of compression speed during tableting scale-up was evaluated. Strain rate sensitivity (SRS) of compactibility profile was examined by evaluating the effect of speed on material deformation behavior. Mechanical parameters, namely Workc/d and tablet recovery (%), were used as measures of irreversible and reversible deformation mechanisms, respectively. It was identified that SRS in compactibility profiles was a result of a higher degree of irreversible deformation that was not offset by a higher degree of elastic recovery. In the second chapter, strain rate sensitivity in the compactibility profile of gabapentin was further analyzed. Surface area analysis, indentation hardness measurements, and consolidation modeling were used to identify the role of compression speed on deformation behavior and internal porous structure of the gabapentin tablets. It was identified that at the faster compression speed, the gabapentin particles showed more fragmentation and formed tablets with smaller pores. In the third chapter, the role of co-processing in improving poor mechanical properties associated with gabapentin tablets was investigated. Co-processed gabapentin consisting of an interactive mixture of gabapentin with \u3c1% Methocel® was compacted into tablets. Enhanced inter-particle bonding and reduced die friction as a result of surface modification improved gabapentin’s tableting properties. Co-processed gabapentin showed improvement in tablet tensile strength and reduction in strain rate sensitivity and tablet capping

Understanding Deformation Behavior and Compression Speed Effect in Gabapentin Compacts

Deformation mechanism and strain rate sensitivity of gabapentin powder was investigated in this work. Heckel analysis, specific surface area and indentation hardness measurements revealed an intermediate yield pressure and brittle fracture as the dominant type of deformation mechanism during consolidation. Strain rate sensitivity of gabapentin was studied by compressing it at 1 mm/min and 500 mm/min compression speeds. Gabapentin demonstrated an atypical strain rate sensitivity in compactibility profile (tensile strength vs. solid fraction). Compacts of gabapentin compressed at fast speed showed an increase in tensile strength when compared with those compressed at slow speed. To understand the effect of compression speed on gabapentin\u27s compactibility, PXRD analysis, surface area analysis, indentation hardness measurements, and consolidation modeling were performed. PXRD analysis carried out on compacts revealed no effect of speed on the physical solid-state stability of gabapentin. Specific surface area of compacts made at fast speed was higher than that of compacts made at slow speed. Indentation measurements performed on gabapentin compacts showed higher values of hardness in the case compacts made at fast speed. It was identified that at the fast compression speed, gabapentin shows greater particle fragmentation and form compacts with smaller pores