Abstract
Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. However its fundamental disadvantage is its fragmentation during direct compression, producing mechanically weak tablets. The primary aim of this study was to assess the fracture behaviour of crystalline mannitol in relation to the energy input during direct compression, utilising ball milling as the method of energy input, whilst assessing tablet characteristics of post-milled powders. Results indicated that crystalline mannitol fractured at the hydrophilic (011) plane, as observed through SEM, alongside a reduction in dispersive surface energy. Disintegration times of post-milled tablets were reduced due to the exposure of the hydrophilic plane, whilst more robust tablets were produced. This was shown through higher tablet hardness and increased plastic deformation profiles of the post-milled powders, as observed with a lower yield pressure through an out-of-die Heckel analysis. Evaluation of crystal state using x-ray diffraction/differential scanning calorimetry showed that mannitol predominantly retained the β-polymorph; however x-ray diffraction provided a novel method to calculate energy input into the powders during ball milling. It can be concluded that particle size reduction is a pragmatic strategy to overcome the current limitation of mannitol fragmentation and provide improvements in tablet properties.
Highlights
Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability
Theoretical energy calculations showed that mill speed was the most influential factor in increasing the energy input during each milling cycle, with powders processed at 400 rpm experiencing an eight fold increase in energy input compared to 200 rpm; whereas doubling the milling time and ball-to-powder weight ratio (BPR) resulted in doubling of the theoretical energy input
This was because the theoretical calculations included limitations in that they were calculated based on ideal conditions, where it had to be assumed that the heating of the vial was negligible; the powder was only affected by energy transfer from the balls to the grinding media and that the majority of energy input occurred during the collision of the balls against the powder along the wall of the vial
Summary
Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. A polyol isomer of sorbitol, is one of the most widely used fillers/diluents in ODTs as it has sweet taste and cooling effect within the mouth upon its disintegration, whilst being non-hygroscopic, minimising moisture uptake in to the tablet during storage[7] It is widely employed within ODT formulations in high concentrations[8], its main disadvantage is that it fragments under compaction resulting in mechanically weak and friable tablets[9,10]. Particle size reduction through high energy input was used to assess the fracture behaviour of mannitol and to develop an understanding of the fragmentation of the excipient during the tableting process. Compressibility was evaluated, with a view to investigating a pragmatic strategy to overcome the limitation of particle breakdown and widen the use of mannitol in various solid dosage forms
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