Effects of Temperature and Pressure During Compression on Polymorphic Transformation and Crushing Strength of Chlorpropamide Tablets

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Abstract
The effects of temperature on the polymorphic transformation of chlorpropamide during compression and on the physical properties of the tablet have been investigated. A heater and liquid nitrogen pool were mounted on the die of a single punch eccentric tableting machine, and the die temperature was controlled by a thermocontroller. A tableting machine with two load cells (upper and lower punches) and a non-contact displacement transducer were used to measure compression stress, distance and energy. The X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The amount of form C transformed from form A at 45°C was about twice that at 0°C with the same compression energy. The amount of form A transformed from form C by compression at 45°C was almost the same as that at 0°C. This suggests that the mechanochemical effect of form A depended on the compression temperature, but that of form C was independent of temperature. The crushing strength of tablets of form A was about twice that of form C, even at the same porosity. The plots of log (crushing strength of tablet) against porosity of form A tablets compressed at 0 and 45°C were linear with the same slope; the slope for form C tablets compressed at 45°C was less than that at 0°C.