Suspension crystallization advantages

A further advantage of solid layer crystallization is that, besides pumps, no moving parts are needed in such processes, since only liquids are transported. A weak point of solid layer crystallization processes is the batchwise or quasicontinuous operating mode. This is different from most suspension crystallization processes that are continuous. 

Suspension crystallization is capable of producing very pure crystals mostly in a continuous operating mode, which is an advantage compared to the most batch solid layer crystallization processes. Another positive feature compared to solid layer crystallization is the better purification per process step and hence a less number of process steps usually with respect to crystallization. Therefore, suspension crystallization plants need in principle less energy compared to solid layer processes. Whether the investment costs of such plants are smaller as well depends on the complexity of the moving parts in suspension plant concepts compared to solid layer concepts (no moving parts, except pumps). 

Knowledge of polymorphic forms is of importance in preformulation because suspension systems should never be made with a metastable form (i.e., a form other than the stable crystal form). Conversely, a metastable form is more soluble than a stable modification, and this can be of advantage in dissolution [Eq. (9)]. There are two types of polymorphism, a fact illustrated in the following discussion. 

In this connection, the use of insoluble agents as photosensitizers seems promising. This approach, in particular, has been realized in respect to the suspension of crystal fullerene C60 (Kasermann and Kempf, 1997, 1998). Its marked advantage is that there are no byproducts of the destruction of fullerene and the compound can be easily removed from the solution by centrifugation. The high efficiency of C60 in viral inactivation has been demonstrated for specific enveloped viruses such as Semliki forest vims (SFV) and vesicular stomatitis vims (VSV) (Kasermann and Kempf, 1997, 1998). The inactivation was achieved in a model system where the vims was suspended in a saline buffer solution. The addition of 2% bovine serum albumin did not affect the kinetics of the photoinactivation of the vims. 

Several solid-state photochemical reactions have been investigated with polycrystalline samples suspended in solvents. Solvents such as water, where the reactant and the product are likely to be insoluble, are usually chosen and a surfactant is added to maintain the suspension. There are at least two apparent advantages to this method. First of all, photochemical equipment commonly used for fluid samples can be readily adopted to solid-state reactions. Secondly, it is expected that all microcrystals in a powdered sample will be homogeneously exposed to the incident light in a well-stirred reactor. Interestingly, while several examples of solid-to-solid reactions in suspended crystals have been documented, there are some cases where the solvent is incorporated into the phase of the final product. In a report by Nakanishi et al. [134] it was shown that p-formyl cinnamic acid (51, Scheme 33) forms mirror-symmetric dimers. While irradiation of crystals suspended in hexane gave amorphous cyclobutanes in 85% yield, suspension of the crystals in water gave a 100% yield of a crystalline photodimer with one water molecule of crystallization. 

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