Mannitol hydration

Yu L, Milton N, Groleau EG, Mishra DS, Vasickle RE. Existence of a mannitol hydrate during freeze-drying and practical implications. J Pharm Sci 1999 88 196-198. 

Mannitol, a frequently used excipient, shows complexity in its application. Yu et al. [1.148] reported the formation of a metastable mannitol hydrate during freeze-drying. The amount of mannitol hydrate varies from vial to vial in one batch. It reduces the... 

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]. 

Table IV. Hydration Numbers and Hydration Time Ratio for Sorbitol and Mannitol...

Recent 620.6 MHz nmr results on sorbitol and mannitol (9) confirm that sorbitol rotates more freely in water than mannitol. This suggests that there is less solute-solvent interaction in sorbitol. Calorimetric results (J ) predict that sorbitol and mannitol should have hydration behavior similar to that described above. Those workers, however, referred to structure breaking properties, even though no structural data was obtained. 

The hydration values for MTHP are different than those for sorbitol and mannitol. This is not surprising since most molecular properties are quite different. This result depends on the model since all were studied with the same simulation procedure. 

Organic nonelectrolytes (neutral molecules, chloral hydrate, hydrocortisone, testosterone, mannitol, etc.) approximately 15%... 

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. 

The platinum complexes appear to synergize with certain other anticancer drugs. Aggressive hydration with intravenous saline infusion alone or with saline and mannitol or other diuretics appears to significantly reduce the incidence of nephrotoxicity. 

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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