Determination of glass transition of the freeze concentrate for lyophilization using novel ex situ supersaturation technique

Determination of the glass transition for a drug freeze concentrate is important to develop a robust lyophilization cycle. In this study, differential scanning calorimetry was utilized to determine the glass transition of the freeze concentrate of decitabine, a sparingly water soluble drug. Different protocols, varying in terms of solute concentration, heating/cooling rate, annealing, quench cooling and ex situ supersaturation, were employed. However, only ex situ supersaturation and quench cooling could detect event related to drug during DSC studies. Ex situ supersaturation protocol detected the glass transition of the freeze concentrate at −12.8 °C. In contrast, quench cooling determined a lower critical process temperature (−31.2 °C), presumably due to presence of higher unfrozen water content. This study has practical implications in determination of the thermal events for optimization of the lyophilization cycle.

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► A comparative analysis of different methods for determination of glass transition of the freeze concentrate is undertaken.
► A novel method for determination of glass transition of the freeze concentrate is described.
► Importance of assessing the critical process temperature of each component of the formulation is envisaged.