Effects of temperature and pressure during compression on polymorphic transformation and crushing strength of chlorpropamide tablets.

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 degrees C was about twice that at 0 degree C with the same compression energy. The amount of form A transformed from form C by compression at 45 degrees C was almost the same as that at 0 degree 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 degrees C were linear with the same slope; the slope for form C tablets compressed at 45 degrees C was less than that at 0 degree C.