Amorphization during Drying

A partial or complete amorphization can occur during drying, either via a desolva-tization or by a mechanical action. 

It has been observed in many cases that the thermal desolvatization results in a partial or complete amorphization. It should be noted that this process does not need to be upscalable. 

The mechanical action in a nutsche type of dryer has been observed to lead to a partial amorphization. 

Static and agitated dryers can have an influence on the particle size distribution of the product. 

The scale-up of the mechanical stress especially in paddle dryers is currently not possible because the bed height on large scale can only be mimicked by larger stirrer tip speed on small scale leading to a somewhat similar shear stress.  

---

During secondary drying, a small RM should be reached, since Tg of the dry product increases with decreasing water content. Tg- of amorphous, freeze dried sucrose increases from 16 °C with 8.5 % RM to 63 °C or 64 °C between 1.0 and 0.7 % RM. It should be taken into account, that RM cannot be taken only at the end of drying, but a possible increase during storage by water desorbed from the stopper has to be considered (see Section 1.3.2 and Pikal et al. [3.7]). 

Recent studies have demonstrated that the chemical homogeneity of the freeze-dried precursor in many cases has no decisive influence on its thermolysis mechanism. It is well known that thermal decomposition of solid solutions of salts can lead to the formation of individual oxides instead of complex oxide compounds. Similar phenomena were observed during thermal decomposition of amorphous freeze-dried precursors in spite of their high chemical homogeneity. " Meanwhile, the small grain size of thermolysis products and their high reactivity resulted in the fast synthesis of complex oxides soon after thermal... 

Spray dryers can produce small crystals through the rapid evaporation of solvent. This operation can lead to the formation of amorphous solids. Spray drying of solutions of abecarnil (see Figure 12.3) produced the least stable polymorph, the B-form crystals [29], The formation of this polymorph was attributed to the high degree of supersaturation reached during drying. 

Four modifications of cimetidine were prepared as phase-pure materials, and each was found to be stable during dry storage [16]. The milling process enabled the conversions of Forms B and C to Form A, while Form A transformed into Form D only upon nucleation. In all cases, the particle size reduction step resulted in substantial formation of the amorphous phase. Compression of the various forms into compacts did not yield any evidence for phase conversion. 

Recent studies on catalyst preparation focused on the impact of drying on the nature of the metal phase on the solid support (amorphous or crystalline) and on the size of the metal particles. For example, for Cu/SiOj catalysts, Toupance et al. [50] found that the drying conditions may have a strong influence on the size of the metal particles. They showed that for this particular case, chemical bonding between the metal and the support may develop during drying. 

---