Physical Ageing of Amorphous Indapamide Characterised by Differential Scanning Calorimetry.

Agata Drogoń,Marcin Skotnicki,Agnieszka Skotnicka,Marek Pyda

doi:10.3390/pharmaceutics12090800

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 (Tg). No ageing occurred at 35, 40 and 45 °C at the measured lengths of times. Molecular relaxation time constants (τKWW) 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 Tg 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 Cp baselines of solid and liquid states of IND, were integrated and enthalpy was presented as a function of temperature.

Highlights

Active pharmaceutical ingredients (APIs) may exist in a crystalline or amorphous form
In order to obtain the amorphous form of indapamide, the samples were heated to 190 ◦ C and subsequently cooled down to 25 ◦ C
The results of the enthalpy relaxation were fitted to the KWW equation, and the parameters describing the kinetics of the ageing process of amorphous IND, such as the relaxation time τKWW and β parameter, were obtained

Summary

Introduction

Active pharmaceutical ingredients (APIs) may exist in a crystalline or amorphous form. The solubility of an amorphous API can be 1.1- to 1000-fold higher in comparison to their crystalline counterpart [1,2,3,4,5,6]. Amorphous forms of drugs usually dissolve more readily and are more bioavailable than their crystalline counterparts, and for that reason, a growing interest in the development of amorphous formulations has been seen [6]. The glass transition temperature (Tg ) is an important physical parameter of amorphous materials, as it indicates a border between a solid and liquid phase of low and high molecular mobility, respectively; the glass transition temperature implies the conditions for the storage of amorphous API [1,6]. The disordered structure of vitreous materials stored below the Tg

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