THE USE OF ISOTHERMAL MICROCALORIMETRY IN THE STUDY OF CHANGES IN CRYSTALLINITY OF SPRAY-DRIED SALBUTAMOL SULFATE

Isothermal microcalorimetry has been used to monitor the recrystallisa tion of spray-dried salbutamol sulphate. The drug recrystallises in wa ter vapour, by a cooperative process. The cooperative nature demonstra tes that the water must first absorb to saturate the entire powder bed before recrystallisation occurs. Consequently, recrystallisation is s lower for low humidities, due to a slower arrival of water vapour. The data have been compared with previous data for recrystallisation of s pray-dried lactose. The heat change for the crystallisation was signif icantly lower for salbutamol sulphate than for lactose. In terms of ap parent enthalpy of crystallisation, the large exothermic responses are indicative of the fact that the crystal form is the thermodynamically stable state. The salbutamol which had been recrystallised at the low er humidities showed that the process, whilst being rapid, was discont inuous. In each case, the exothermic recrystallisation was followed by an endothermic response for the expulsion of water as the amorphous r egion recrystallised. There was a repeating sequence of crystallisatio n, followed by water expulsion, followed by further recrystallisation. With each repeat of the cycle the responses decreased in size. This a bility to follow crystallisation in real time provides a novel insight into the process.