Physical Ageing of Amorphous Indapamide Characterised by Differential Scanning Calorimetry

Agata Drogoń; Marcin Skotnicki; Agnieszka Skotnicka; Marek Pyda

doi:10.3390/pharmaceutics12090800

Physical Ageing of Amorphous Indapamide Characterised by Differential Scanning Calorimetry

Pharmaceutics. 2020 Aug 25;12(9):800. doi: 10.3390/pharmaceutics12090800.

Authors

Agata Drogoń¹, Marcin Skotnicki², Agnieszka Skotnicka², Marek Pyda^{1

3}

Affiliations

¹ Department of Chemistry, Rzeszów University of Technology, 35-959 Rzeszów, Poland.
² Department of Pharmaceutical Technology, Poznań University of Medical Sciences, 60-780 Poznań, Poland.
³ Department of Biophysics, Poznań University of Medical Sciences, 60-780 Poznań, Poland.

Abstract

The objective of this study was to characterise amorphous indapamide (IND) subjected to the physical ageing process by differential scanning calorimetry (DSC). The amorphous indapamide was annealed at different temperatures below the glass transition, i.e., 35, 40, 45, 65, 75 and 85 °C for different lengths of time, from 30 min up to a maximum of 32 h. DSC was used to characterise both the crystalline and the freshly prepared glass and to monitor the extent of relaxation at temperatures below the glass transition (T_g). No ageing occurred at 35, 40 and 45 °C at the measured lengths of times. Molecular relaxation time constants (τ^KWW) for samples aged at 65, 75 and 85 °C were determined by the Kohlrausch-Williams-Watts (KWW) equation. The fragility parameter m (a measure of the stability below the glass transition) was determined from the T_g dependence from the cooling and heating rates, and IND was found to be relatively stable ("moderately fragile") in the amorphous state. Temperature-modulated DSC was used to separate reversing and nonreversing processes for unaged amorphous IND. The enthalpy relaxation peak was clearly observed as a part of the nonreversing signal. Heat capacities data for unaged and physically aged IND were fitted to C_p baselines of solid and liquid states of IND, were integrated and enthalpy was presented as a function of temperature.

Keywords: amorphous drugs; differential scanning calorimetry; enthalpy relaxation; fragility; indapamide; physical ageing.