Quantifying crystallisation rates of amorphous pharmaceuticals with dynamic mechanical analysis (DMA)

One of the stability concerns for amorphous pharmaceuticals is phase transformation to a crystalline form. Since conversion from an amorphous matrix to a crystalline lattice should result in a change in mechanical modulus of the material dynamic mechanical analysis (DMA) offers potential as a stability-indicating assay for what are often complex formulations. Amorphous indomethacin glasses were used as model samples. Pockets made of a metal weave allowed the glass to be mounted in the instrument while ensuring exposure to RH. Crystallisation was manifest as an increase in the storage modulus signal with time. Conversion of the data to fraction crystallisation allowed quantitative determination of the rate and mechanism of crystallisation by application of the Urbanovici-Segal model. Rates of crystallisation were seen to increase with temperature and humidity while temperature and humidity affected the mechanism of crystallisation. High temperature and humidity resulted in three dimensional crystal growth. Reducing the humidity caused a switch in mechanism to growth from edges. Reducing temperature resulted in a mixed mechanism of growth from surfaces and edges. The DMA was also sensitive to crystallisation of phenobarbital sodium formulated in an oral film, but quantitative analysis was not possible as the onset of crystallisation was not recorded.