Sergey Vyazovkin1, Ion Dranca. 1. Department of Chemistry, University of Alabama at Birmingham, 901 S. 14th Street, 35294, USA. vyazovkin@uab.edu
Abstract
PURPOSE: This study was conducted to demonstrate the use of differential scanning calorimetry (DSC) in detecting and measuring beta-relaxation processes in amorphous pharmaceutical systems. METHODS: DSC was employed to study amorphous samples of poly(vinylpyrrolidone) (PVP), indomethacin (IM), and ursodeoxycholic acid (UDA) that were annealed at temperatures (T(a)) around 0.8 of their glass transition temperatures (T(g)). Dynamic mechanical analysis (DMA) was used to measure beta-relaxation in PVP. RESULTS: Reheating the annealed samples gives rise to annealing peaks that occur below T(g). The peaks cannot be generated when annealing below the low temperature limit of beta-relaxation. These limits are around 50 degrees C for PVP, -20 degrees C for IM, and 30 degrees C for UDA. The effective activation energy (E) of the sub-T(g) relaxation has been estimated for each T(a) and found to increase with T(a), reflecting increasing contribution of the alpha-process. Estimates of E for beta-relaxation have been obtained from the lowest T(a) data, and are as follows: 68 (PVP), 56 (IM), 67 (UDA) kJ mol(-1). CONCLUSIONS: DSC can be used for detecting beta-relaxation processes and estimating its low temperature limit, i.e., the temperature below which amorphous drugs would remain stable. It can also provide comparative estimates of low temperature stability of amorphous drugs in terms of the activation energies of the beta-relaxation.
PURPOSE: This study was conducted to demonstrate the use of differential scanning calorimetry (DSC) in detecting and measuring beta-relaxation processes in amorphous pharmaceutical systems. METHODS: DSC was employed to study amorphous samples of poly(vinylpyrrolidone) (PVP), indomethacin (IM), and ursodeoxycholic acid (UDA) that were annealed at temperatures (T(a)) around 0.8 of their glass transition temperatures (T(g)). Dynamic mechanical analysis (DMA) was used to measure beta-relaxation in PVP. RESULTS: Reheating the annealed samples gives rise to annealing peaks that occur below T(g). The peaks cannot be generated when annealing below the low temperature limit of beta-relaxation. These limits are around 50 degrees C for PVP, -20 degrees C for IM, and 30 degrees C for UDA. The effective activation energy (E) of the sub-T(g) relaxation has been estimated for each T(a) and found to increase with T(a), reflecting increasing contribution of the alpha-process. Estimates of E for beta-relaxation have been obtained from the lowest T(a) data, and are as follows: 68 (PVP), 56 (IM), 67 (UDA) kJ mol(-1). CONCLUSIONS: DSC can be used for detecting beta-relaxation processes and estimating its low temperature limit, i.e., the temperature below which amorphous drugs would remain stable. It can also provide comparative estimates of low temperature stability of amorphous drugs in terms of the activation energies of the beta-relaxation.