Solution/suspension layering pelletization

Another piece of equipment that has been used to manufacture pellets by solution/suspension layering is the tangential spray or centrifugal granulator. An important parameter that needs to be established early in the process is quantity of starter seeds or cores charged into the machine that should, at the minimum, cover the nozzles during start-up otherwise, the sprayed liquid droplets will either be sprayed onto the wall of the product container or become entrained in the fluidization air. The latter could lead to clogging of the filters, which would then not only increase the pressure differential across the filters and compromise the batch but also may complicate equipment cleanup. In either case, the yield, and probably the quality of the pellets, will be reduced dramatically. As the size of the... 

Solution/suspension layering is usually used when the desired drug loading of the pellets is low because production of high-potency pellets from a low solids content formulation is not economically feasible. An important factor that needs to be considered when suspensions are used as opposed to solutions is the particle size of the drug. Micronized drug particles tend to... 

Jones, D.M. Solution and suspension layering. In Pharmaceutical Pelletization Technology Ghebre-Sellassie, I., Ed. Marcel Dekker, Inc. New York, 1989 Vol. 37, 145-164. 

To a suspension of the ester (3) (0.058 g, 0.16 mmol) in 75% aqueous methanol (2 mL) was added one pellet of potassium hydroxide (0.1 g). The mixture was stirred at 70°C for 1 h during which time the material dissolved. The solution was cooled to room temperature, acidified with 1 N aqueous hydrochloric acid and then extracted with 80% ethyl acetate/hexane. The combined organic layers were dried over anhydrous MgS04, filtered and concentrated to afford a white solid. Recrystallization from dichloromethane/hexane afforded the desired acid (4) as a white, crystalline solid (42 mg, 91%) melting point 230°-231°C. The structure of the product was also confirmed using IR, iH NMR and mass spectroscopy. 

Procedure Packed erythrocytes, washed twice in Hepes buffer, are resuspended in an equal volume of the same buffer. The erythrocyte suspension (2 ml) is carefully layered over the Percoll-diatrizoate solution (2 ml) in a glass centrifuge tube with an internal diameter of 10 mm. After centrifugation at 400 x g for 20 min at room temperature, erythrocytes with normal density are carefully removed from the surface of the Percoll-diatrizoate cushion using a pasteur pipette. This fraction is referred to as the normal density fraction. Erythrocytes with elevated density, which had pelleted below the Percoll-diatrizoate, can then be removed in a similar manner. This latter fraction is referred to as the dense fraction. Finally, each fraction of erythrocytes is washed twice in 10 vol. of Hepes buffer at 4°C. 

Roodyn [17] placed a suspension of liver nuclei in a tube containing several layers, each with a different sucrose concentration. With this method he demonstrated that after centrifugation the succinoxidase activity associated with the nuclear pellet is found in a layer different from the one containing DNA. In contrast, after centrifugation in layered sucrose solution, a large portion of the aldolase associated with nuclear suspension remained with the layer that contained DNA. These findings led Roodyn to conclude that some aldolase activity is native to the nucleus. 

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