Moisture mannitol

Mannitol is used as the dusty coating on chewing gum it keeps the gum from absorbing moisture and getting sticky. This is due to its humectant (moisture-trapping) properties and very low hygroscop-icity (meaning that it does not attract moisture from the air). 

The hydration state of risedronate sodium was monitored continuously in a fluidized bed dryer and correlated to data on the physical stability of tablets made from the monitored material [275]. The final granulation moisture was found to affect the solid-state form, which in turn dictated the drug s physical stability over time. The process of freeze-drying mannitol was monitored continuously with in-line Raman and at-line NIR spectroscopies [276]. The thin polymer solvent coatings, such as poly(vinyl acetate) with toluene, methanol, benzene, and combinations of the solvents, were monitored as they dried to generate concentra-tion/time profiles [277]. 

Experiments using a matrix of four levels of ferulic acid and four levels of moisture stress demonstrated that the combined action was additive under more stressful levels of the individual factors than in the previous tests. Duke et al. (23) tested the germination of lettuce seeds treated with phenolic acids (1 mM) at water potentials (D-mannitol) of 0, -0.2, -0.4, and -0.6 MPa. The combined action of low water potential and exposure to phenolic acids resulted in an additive detriment to germination, and the authors concluded from probit analysis that the mechanism of action from these sources was similar. Whatever their mechanisms, moisture stress and phenolic acids appear to work together in limiting growth of plants. 

Tomohiro Y, Forbes RT, Peter Y, Yoshiaki K. The improved compaction properties of mannitol after a moisture-induced polymorphic transition. Int J Pharma 2003 258(1-2) 121 131. 

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. 

Fig. 1.69.2. Moisture sorption profiles of anhydrous lactose (1), mannitol (2), trehalose (3) and sucrose (4). Top before and bottom after lyophilization (% weight change from the data in Table 1.10.4) at different relative humidity (RH) changes over 50-60 h. Before lyophilization 1, lactose — 1.1 RH 10%, 1.2 RH 60% 2, mannitol 3, trehalose - 3.1 RH 10%,...

Fakes et al. [1.152] described the moisture sorption behavior of mannitol, anhydro-lactase, sucrose, D-(+)-trehalose, dextran 40 and providone (PVP K24) before and after freeze-drying in a 10% solution. All products where frozen at 0.50 °C/min to -40 °C and freeze-dried at 0.13 mbar and Tsh = -15 °C for 28 h. SD lasted for 14 h at Tsh = 25 °C. Table 1.10.5 shows the moisture contents before and after freeze-dying. Figure 1.69.2 present the weight change in % of sucose, trehalose, mannitol and lac-... 

Figure 22, for instance, shows the behavior of a freeze-dried plug of mannitol (residual moisture 1.5%). We can see that, in comparison with the initial solution (at 10% mannitol), the thermoluminescence of the dry material is some 20 times stronger and does not follow the same pattern. The lower peak (at -152°C) is very narrow whereas the higher one (near -118°C) is substantially depressed. This is not surprising if we assume, as we have already done, that the first peak is directly connected to the water molecule itself while the second one seems to be geared to the tridimensional network of the water molecules within the crystalline lattice. 

Figure 5 Effect of excipients on the storage stability of freeze-dried human growth hormone (hGH). Samples were stored for I month at 40°C. Solid bars, aggregation (primarily dimer). Hatched bars, chemical degradation via methionine oxidation and asparagine deamidation. The glass transition temperatures of the initial freeze-dried formulations are given above the bars when a gla.ss transition temperature could be measured by DSC. The glycine mannitol formulation is a weight ratio of hGH glycine mannitol of 1 1 5, the dex-tran formulation is 1 6 hGH dextran 40, none means no stabilizer, and the others are 1 1 hGH stabilizer. All formulations contain sodium phosphate buffer (pH 7.4) at 15% of the hGH content. Initial moisture contents are all ==1%. (Data from [4].)...

Figure 10 The stability of a freeze-dried monoclonal antibody/vinca alkaloid conjugate formulation. Desacetylvinblastine hydrazide is linked to the KSl/4 monoclonal antibody via aldehyde residues of the oxidized carbohydrate groups on the antibody. The formulation is conjugate/glycine/mannitol in a I I I weight ratio. Storage temperatures are 25°C and 40°C for samples with moisture contents of 1.4%, 3.0%, and 4.7%. ( ) Dimer formation. (A) Free vinca generation (hydrolysis). ( ) Vinca degradation. (—) Best fit to the WLF equation. (Reproduced with permission from [54].)...

Fig. 10 Examples of the kinetics of secondary drying. Triangles = mannitol (crystalline) squares = poly (vinylpyrrolidone) circles = moxalactam di-sodium (amorphous). All solids were prepared by freeze-drying a 5% aqueous solution from a 1-cm fill depth, followed by hydration to a uniform moisture level of 7%. The quantity, F, is the fractional attainment of equilibrium, which corresponds to near zero water content. The secondary drying conditions were product temperature = 18°C chamber pressure = 200mTorr. (From Ref °l)...

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