Effects of molecular weight of polyvinylpyrrolidone on the glass transition and crystallization of co-lyophilized sucrose

Abstract

The purpose of the present study was to investigate the effects of molecular weight (MW) of polyvinylpyrrolidone (PVP) on glass transition and crystallization of sucrose. Thus, sucrose was co-lyophilized with 2.5 and 5.0% w/w PVP of different molecular weights, which were characterized using gel permeation chromatography. Freeze drying was carried out for 48 h at a shelf temperature of −40°C and a pressure of about 36 Pa. The samples were then dried in a vacuum oven at 24°C for 12 h before drying for a further 12 h at 40°C. Differential scanning calorimetry (DSC) was employed to measure the glass transition temperature ( T g), dynamic crystallization temperature ( T c) and isothermal crystallization induction time ( t c) at 85°C of sucrose. Isothermal water vapour sorption of each sample was also measured at different relative humidities. T g values of sucrose varied from 48.3±0.8°C for freeze-dried (FD) sucrose alone to 58.8±0.8°C for the mixture containing 5.0% PVP of nominal MW 300 K. PVP increased sucrose T g significantly (ANOVA P<0.05). Although there was no significant difference ( P>0.05) in T g of the mixtures containing 2.5% w/w PVP of different MW, samples with 5.0% PVP of MW 300 K produced a significantly higher ( P<0.05) T g than the other mixtures. All mixtures were shown to possess higher ( P<0.01) T c than FD sucrose alone, which exhibited a T c of approximately 85°C. PVP of MW 300 K consistently induced a significantly ( P<0.05) higher T c of sucrose than PVP of smaller MW. Increasing PVP concentration from 2.5 to 5.0% also resulted in a substantial increase in sucrose T c. Using isothermal water vapour absorption, sucrose t c was found to increase up to over 10 times when it was co-lyophilized with 2.5% PVP, the actual value of t c being dependent upon the MW of the PVP. For example, PVP of MW 300 K resulted in a sucrose t c at 85°C (89.1–95.6 min), which was approximately seven times higher than that of 2.5% PVP of MW 24 or 40 K. A longer t c of sucrose was also observed for mixtures containing PVP of MW 300 K than when sucrose was mixed with PVP of smaller MW. Thus the effect of PVP on sucrose T g, T c and t c was found to be dependent upon MW. PVP of higher MW was more efficient in inhibiting sucrose crystallization and by stabilizing glassy structures of the sugar, these polymers may improve the stability of co-lyophilized proteins and peptides.