Amorphous trehalose

Recombinant human interleukin-6 Aggregation prevented by amorphous trehalose, sucrose or a combination of sucrose, and glycine or mannitol [24]... 

Molecular simulations of cryo- and lyoprotectants could provide valuable insights into the behavior and effectiveness of these molecules. Unfortunately, studies of that nature have been scarce only recently have some reports begun to appear in the literature (Donnamaria et al., 1994 Liu et al., 1997 Conrad and de Pablo, 1999 Roberts and Debenedetti, 1999). In previous work, we have conducted molecular simulations of pure, amorphous trehalose, sucrose, and their aqueous solutions (Conrad and de Pablo, 1999 Ekdawi et al., 2001). 

The results presented in Figures 40.2 and 40.3 suggest that amorphous trehalose partially satisfied the hydrogen bond requirement of the exposed polar group on freeze-dried protein and the residual water supplemented the remaining hydrogen bond requirement. Amorphous trehalose has been believed to efficiently serve freeze-dried protein as a substitute for water (Carpenter and Crowe, 1989 Allison et al., 1999 Crowe, 2002). However, as mentioned above, trehalose, which is larger than water, is not able to cover... 

An interesting use of GVS, for amorphous dispersions, is detection and quantification of crystallinity. Due to higher hygroscopicity of hydrophilic polymers and amorphous API of ASD, the exposure of a sample to elevated humidity environment triggers the sorption of water molecules by polar/hydrophilic functional groups at the air-solid interface. The a-relaxation time of amorphous material often correlates with its water sorption potential (Bhardwaj and Suryanarayanan 2013). The gravimetric vapor sorption (GVS)-desorption led to the dissimilar structurally reversal of annealed amorphous trehalose when compared to that obtained by heating beyond Tg (Saxena et al. 2013). The sorbed water molecules Tg = -137°C) increases... 

Roe KD, Labuza TP (2005) Glass transition and crystallization of amorphous trehalose-sucrose mixtures. Int J Food Prop 8 559-574... 

Surana R, Pyne A, Suryanarayanan R. Effect of aging on the physical properties of amorphous trehalose. Pharm Res 2004 21(5) 867-874. 

A. Simperler, A. Komherr, R. Chopra, W. Jones, W. D. S. Motherwell and G. Zifferer. The glass transition temperatures of amorphous trehalose-water mixtures and the mobility of water An experimental and in silico study. Carbohydr. Res. 342, 2007, 1470-1479. 

The effect of physical aging on the crystallization state and water vapor sorption behavior of amorphous non-solvated trehalose was studied [91]. It was found that annealing the amorphous substance at temperatures below the glass transition temperature caused nucleation in the sample that served to decrease the onset temperature of crystallization upon subsequent heating. Physical aging caused a decrease in the rate and extent of water vapor adsorption at low relative humidities, but water sorption could serve to remove the effects of physical aging due to a volume expansion that took place in conjunction with the adsorption process. 

Studies with the freeze dried DPPC liposomes in trehalose solution showed, that not Tg )f the amorphous sugar is the critical temperature during storage, but the bilayer transition emperature Tm. for the lyposomes determines the short term stability of the formulation. With trehalose as lyoprotectant and a low residual water content, Tm proved to be 10 to 30 °C below the onset of T . 30 min heating above Tm but well below T% decreased the retention of CF after rehydration. Tm< after the heating was reduced from 40 to 80 °C to below 25 °C. 

Table 1.6.1 Glass transition temperature Tg and crystallization temperature Tc for amorphous sucrose, trehalose, lactose, raffinose and amorphous sucrose in the presence of absorbed water...

Fakes et al. [1.152] evaluated the moisture sorption behavior of mannitol, anhydrous lactose, sucrose, D-(+)-trehalose, dextran 40 and povidine (PVP K24) as bulking agents. Mannitol was found to be crystalline and non-hygroscopic before and after freeze-drying with RM 0.1-0.3% w/w at 25 °C and 10-60% RH. Anhydrous lactose, sucrose and trehalose were crystalline and relatively non-hygroscopic with RM 0.86, 0.15 and 9.2% respectively. After freeze-drying they where amorphous with RM 1.6, 2.5 and 1.2%, respectively, and adsorbed moisture in an increasing RH atmosphere. Lactose adsorbed 10% water and formed its crystalline hydrate at 55% RH. 

Recombinant human growth hormone (rhGH) Mannitol and glycine as amorphous excipients to prevent human growth hormone (hGH) aggregation. Trehalose as a lyoprotectant, reserves the secondary structure of rhGH. [14]... 

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