SELF HEATING OF TABLETS
Tablets containing a drug substance and a small amount of an incipient were routinely film-coated and then dried in a stream of air at about 90°C. They were then discharged from the drier into kegs. On one occasion, several hours after discharge, the room was found to be filled with fumes and it was apparent that most of the tablets in one keg had decomposed. Careful examination of the contents indicated that the greatest decomposition occurred in the centre of the keg. The active substance was known to be self reactive, as adiabatic calorimetry had shown that it decomposed vigorously with an onset at about 100°C. Recommendations on handling the substance had not been extended to the tablet blend and a subsequent test showed that the tablets behaved similarly. (The mixture might have had a lower onset temperature).
There was sufficient evidence to conclude that the tablets in this particular keg had been heated excessively (time or temperature) but this would appear to be the most likely cause of the incident. The pure active substance has been the subject of earlier self heating incidents during granulation and milling, where abnormal conditions caused an accumulation of the heat produced in the process.
Other factors that have been implicated in similar incidents with other substances include:
- An increase in the pack size
- An increase in the ambient temperature
Both these factors decrease heat losses and allow more heat to accumulate. It is essential that information concerning the reactivity of substances is understood by all who are involved with the handling, storage, and transport of products containing the substance.