Ion Dranca

Probing Beta Relaxation in Pharmaceutically Relevant Glasses by Using DSC

PurposeThis study was conducted to demonstrate the use of differential scanning calorimetry (DSC) in detecting and measuring β-relaxation processes in amorphous pharmaceutical systems.MethodsDSC was employed to study amorphous samples of poly(vinylpyrrolidone) (PVP), indomethacin (IM), and ursodeoxycholic acid (UDA) that were annealed at temperatures (Ta) around 0.8 of their glass transition temperatures (Tg). Dynamic mechanical analysis (DMA) was used to measure β-relaxation in PVP.ResultsReheating the annealed samples gives rise to annealing peaks that occur below Tg. The peaks cannot be generated when annealing below the low temperature limit of β-relaxation. These limits are around 50°C for PVP, −20°C for IM, and 30°C for UDA. The effective activation energy (E) of the sub-Tg relaxation has been estimated for each Ta and found to increase with Ta, reflecting increasing contribution of the α-process. Estimates of E for β-relaxation have been obtained from the lowest Ta data, and are as follows: 68 (PVP), 56 (IM), 67 (UDA) kJ mol−1.ConclusionsDSC can be used for detecting β-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 β-relaxation.

Implications of Global and Local Mobility in Amorphous Sucrose and Trehalose as Determined by Differential Scanning Calorimetry

PurposeTo investigate the local and global mobility in amorphous sucrose and trehalose and their potential implications on physical stability.MethodsAmorphous sucrose was prepared by lyophilization while amorphous trehalose was prepared by dehydration of trehalose dihydrate. The variation in the effective activation energy of α-relaxation through glass transition has been determined by applying an isoconversional method. β-Relaxations were detected as shallow peaks, at temperatures below the glass transition temperature, caused by annealing glassy samples at different temperatures and subsequently heating at different rates in a differential scanning calorimeter. The effect of heating rate on the β-relaxation peak temperature formed the basis for the calculation of the activation energy.Resultsα-Relaxations in glassy trehalose were characterized by larger activation energy barrier compared to sucrose, attributable to a more compact molecular structure of trehalose. The effect of temperature on viscous flow was greater in trehalose which can have implications on lyophile collapse. The size of the cooperatively rearranging regions was about the same for sucrose and trehalose suggesting similar dynamic heterogeneity at their respective glass transition temperatures. The activation energy of β-relaxations increased with annealing temperature due to increasing cooperative motions and the increase was larger in sucrose. The temperature at which β-relaxation was detected for a given annealing time was much less in sucrose implying that progression of local motions to cooperative motions occurred at lower temperatures in sucrose.ConclusionsTrehalose, having a lower free volume in the glassy state due to a more tightly packed molecular structure, is characterized by larger activation energies of α-relaxation and experiences a greater effect of temperature on the reduction in the activation energy barrier for viscous flow. The pronounced increase in cooperative motions in sucrose upon annealing at temperatures below (Tg −50) suggest that even a small excursion in temperature could result in a significant increase in mobility.