To predict the crystallization time of amorphous solid dispersions by controlling the combined effect of temperature and moisture content.Methods
The authors exposed amorphous samples of spray-dried API and Hydroxypropylmethylcellulose Phtalate to various temperature and humidity conditions below and above the glass transition temperature (Tg) until crystallization of the API was observed. The crystallization of API was detected by XRPD, while the Tg and the water absorption by the amorphous dispersion are quantified by mDSC and water sorption analysis.Results
Extrapolation of the data obtained at a temperature above Tg to conditions below Tg gives only a qualitative trend. By contrast, in conditions below Tg the logarithm of onset of crystallization time was shown to vary linearly with the Tg/T ratio. A statistical analysis shows that the data obtained in the highest temperature/humidity conditions, for which the onset of crystallization is below 3 months, can be extrapolated over 15 months.Conclusions
The proposed methodology can be used as a stress program to predict long-term stability from a relatively short observation period and to design appropriate temperature and humidity conditions for long-term storage to prevent crystallization.
To access the full text, please Sign in
If you have institutional access, please click here