Effects of Environmental Temperature and Compression Energy on Polymorphic Transformation During Tabletting

The effects of temperature on the polymorphic transformation and the compression of chlorpropamlde forms A and C during tabletting were investigated by X-ray diffractometry. The X-ray diffraction profiles of the sample powders deagglomerated after compression were recorded to calculate the degree of polymorphic transformation. A single punch eccentric tabletting machine equipped with two load cells (upper and lower punches) and with a noncontact displacement transducer was used to measure the compression stress, energy and distance between punches. A heater and a liquid nitrogen pool were mounted on the die of the tabletting machine, and the die temperature was controlled with a thermocontroller. Two types of compression methods, multi-tabletting at room temperature and single tabletting at 0-45°C, were used in the present study. In the first method, the stable form A or metastable form C was loaded in to the die and the sample was compressed with a compression stress of 196 MPa. Compression was repeated from 1 to 30 times. The results for forms A and C suggested that both forms were mutually transformed, and that the content of forms A and C reached equilibrium above 100 J/g of compression energy after more than 10-times compression. After 30-times compression, the content of A, C, and the noncrystalline solid form were almost constant at about 45%, 25% and 30%, respectively. The compression energy was estimated to be 500-600 J/g. In the second method, single tabletting at 0° and 45°C, the amount of form C transformed from form A at 45°C was about two times larger than that at 0°C at the same compression energy. The amount of form A transformed from form C at 45°C was almost the same as that transformed at 0°C. This suggests that the mechanochemical stability of form A was affected by compression temperature, while that of form C was independent of temperature. The crushing strength (CS) of from A tablet was about two times higher than that of form C even at the same porosity. The relationships between log (CS) of form A tablets compressed at 0 or 45°C and porosity showed straight lines with the same slope, but the slope for form C tablets compressed at 45°C was smaller than that for those compression at 0°C. From these results it appears that the transformation mechanism of forms A and C during compression was as follows: Form A or C was converted to a noncrystalline solid by mechanical energy, and then the solid was transformed into form A or C. The transformation of every form was affected by the environmental temperature.