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Recovery

Typical recovery methods are described below.

Distillation

Distillation is a thermal process used to separate liquid species by evaporation. Batch, flash, and fractional distillation columns are used in API processing. In batch distillation the composition of the material inside the column varies as the process continues and the volume drops. As a result of the volume drop there is a loss of heat transfer surface which causes the efficiency of the equipment to decrease. To counter this drop in heat transfer surface a heat exchanger is often used to provide an external surface as the product is pumped through it. Flash distillation is a process that uses a single stage column with one material while fractional distillation uses multiple materials. Often vacuum pumps are attached to the distillation columns so that evaporation can occur at lower temperatures since often materials in API processing can be heat sensitive.

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(Copyright GEA Process Engineering Inc.,Columbia, MD)

Membranes

In the pharmaceutical industry membrane processes such as pressure-driven and are normally used. One of the common ways membranes are used in this industry is by direct flow filtration. This involves passing the feed solution through a membrane, where particles are retained by physical capture or absorption. These membranes are commonly available in cartridges that contain the membrane or can be found as disposable capsules. The main problem with direct flow membranes is that over time they get built-up with particles that reduces the effective membrane area and can cause contamination of the drug if not addressed. The way to overcome these factors is using tangential flow filtration. In this process the feed stream runs parallel over the membrane to separate the particles. These membranes can be cleaned easier and have longer lifetimes than membranes used in direct flow filtration.

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(Copyright GEA Process Engineering Inc.,Columbia, MD)

Crystallizers

The final API is often in the solid stage in most synthetic processes. Crystallization is a category that groups a variety of processes for solid isolation, which includes cooling, evaporation, concentration, reaction precipitation, pH change precipitation, and solvent change precipitation. These actions are performed using a batch crystallizer , which is basically a modified batch reactor. This crystallizer allows agitation and heat transfer adjustments to avoid damage of the final solid product. Often materials of the desired crystal type are added at the appropriate time to initiate the processes in the direction of the desired final product. This process can also be carried out with a continuous crystallizer but this is less common in API manufacturing.

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(Copyright Sulzer Chemtech Ltd., Switzerland)

Filters

After a solid is produced it can be separated from the liquid by filtration. A calmic or bag filter can be used to remove small quantities of solid but for larger quantities a is used. The original single sheet nutsche filter was simply a box that had a vacuum attached at the bottom to draw the filtrate through the filter medium. The problem with this design is that there is nothing to protect the operator from the contents inside of the box as well as protecting the contents from contamination. For this reason an agitated pressure nutsche filter is more common in API manufacturing. This design uses a pressurized chamber above the filter medium where the filter cake is smoothed using an agitation arm. A vacuum is used to pull the filtrate out of the cake or pressure can be applied to the top to create a pressure difference. After the filtrate is removed the cake is washed inside the filter, so that the vacuum can pull it out of the cake, to remove soluble impurities. From this step the solid cake can be removed from the filter for drying. Sometimes the nutsche pressure filter can be used to dry the cake as well by passing hot water through coils along the body of the filter. This way the material does not have to risk contamination being transported to a separate dryer but this process can be a limiting time factor for the plants.

Centrifuges

The principle of a centrifuge is to create enough centrifugal force to push the liquid through a filter medium which separates it from the solid. There are four types of centrifuges used in API manufacturing. The vertical axis with a top discharge centrifuge is mainly used for small quantities because the operator can get exposed to material when discharging it by removing a basket. The other vertical axis centrifuge uses a plough to push the material out of the basket and into a chute at the bottom. The horizontal axis centrifuges can spin at higher speeds than the vertical axis centrifuges and are often preferred since they provide a higher centrifugal force to drive the liquid out. Ones that use a peeler discharge discharge the solid by using a peeler blade that pushes the solid into a chute. The inverting bag discharge removes the solid by simply inverting the filter medium to create a bag.

centri.JPG

(Copyright Alfa Laval, Richmond, VA)

Acknowledgements

Alfa Laval , Richmond, VA

GEA Process Engineering Inc. , Columbia, MD

Sulzer Chemtech Ltd. , Switzerland

Water Technologies Business Unit of Siemens Industry, Inc. , Warrendale, PA

References

Bennett, Bill and Cole, Graham. Pharmaceutical Production: An Engineering Guide. United      Kingdom: The Institution of Chemical Engineers, 2002. Print.

Pabby, Anil Kumar. Handbook of Membrane Separations: Chemical, Pharmaceutical, Food, And      Biotechnological Applications. Boca Raton: CRC Press, 2009.

Developers

Thomas Plegue

Howard Hsu