Crystallization precipitation versus

Aluminum sulfate is a starting material in the manufacture of many other aluminum compounds. Aluminum sulfate from clay could potentially provide local sourcing of raw materials for aluminum production. Processes have been studied (24) and the relative economics of using clay versus bauxite have been reviewed (25). It is, however, difficult to remove impurities economically by precipitation, and purification of aluminum sulfate by crystallization is not practiced commercially because the resulting crystals are soft, microscopic, and difficult to wash effectively on a production scale (26—28). 

Coordinated Phosphate Method. In this method of treatment, no free caustic is maintained in the boiler water. Fig. 10 shows the phosphate concentration versus die resulting pH when trisodium phosphate is dissolved in water. Recent laboratory tests show that the crystals which precipitate from a concentrated solution of trisodium phosphate at elevated temperatures contain disodium phosphate and that the supernatant liquid is rich in sodium hydroxide. The sodium hydroxide can destroy the magnetite protective film on boiler surfaces. To assure that no free caustic is present, a boiler-water phosphate concentration thal corresponds Lo a sodium-lo-phosphate mole-ratio of 2.6 is recommended above 1000 psi (68 atm), as... 

An example of this approach is illustrated in Fig. 3.4. The graph in the center is a two-dimensional slice of a four-dimensional surface over which [protein], ([protein] X [precipitant]), pH, and temperature were varied, in attempts to find optimal crystallization conditions for the enzyme tryptophanyl-tRNA synthetase. Note that this surface samples the rectangular region [protein] versus ([protein] X [precipitant]), mentioned earlier. The height of the surface is the score for the crystallization. Surrounding the graph are photos of typical crystals obtained in multiple trials of each set of conditions. None of the trial conditions were near the peak of the surface. The... 

The conditions used in the hydrochloride formation/crystallization step were somewhat different when MIBK/water was used in place of ethyl acetate. In particular, hydrochloride formation needed to be carried out by adding concentrated hydrochloric acid to the MIBK solution of dilevalol base at ca. 55°C (versus ca. 25°C for ethyl acetate). In this way, oiling out of the hydrochloride salt was avoided. A small amount of citric acid was included in the crystallization system to chelate any traces of iron which may be introduced. The amount of water in the system is more than sufficient to dissolve the small amount of citric acid—in early versions of the process, using much less water, precipitation of some citric acid caused a slight discoloration of the dilevalol hydrochloride. The crystallization conditions were carefully chosen to produce a crystal which filtered and washed well, which dried well (to MIBK <0.5%) and which gave a bulk density (ca. 0.3 g/ml) which met Pharmaceutical Development s criteria for operation of their tabletting process. 

Once prenucleation, nucleation, and post-nucleation processes have resulted in a stable nuclei population—or if seeding material is available—the final size of the precipitate from a batch precipitation process can be controlled via manipulation of the reactant feed rate versus time profile. This concept is described in details and illustrated with an example for submicron crystals of AgBr. 

Rapid form dissociation and precipitation of known forms of the parent celecoxib was observed in 0.1 N HCl, SGF, 0.02 N HCl, pH 6.5 phosphate buffer and pH 6.5 phosphate buffer with sodium dodecyl sulfate (SDS). The initial dissolution rate was found to be superior for the co-crystal versus the stable form of the parent compound, but rapid conversion to aggregated crystalline celecoxib made this co-crystal a poor candidate for direct use as a dosage form. This initial dissolution advantage was exploited further by formulating the co-crystal with PVP-K30 and the ionic surfactant SDS. Using this combination of excipients, the co-crystal was repeatedly observed to precipitate as a poorly crystalline mixture of metastable celecoxib form 4 and amorphous material. Although the co-crystal was not tested in vivo, the in vitro performance improvements are consistent with improvements observed in other celecoxib formulations with demonstrated in vivo advantages over Celebrex . 

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