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Pharmaceuticals: Tablet Manufacturing

In pharmaceutical tablet manufacturing the API is first granulated to a fine particle. Once properly granulated, the particles are compressed to form the basic structure of the tablet. Lastly, a coating is applied to the tablet to hold the particles together.

Click on the pictures below to navigate through the tablet manufacturing process.

Granulation

Granulation is the first step in the development of the dry product. The drug substance created in the bulk product step is blended with binders, fillers, coloring materials and lubricants. This operation increases the density and uniformity of the mixture for the compression process. There are three types of granulation that are used in pharmaceutical manufacturing: dry, wet, and spray granulation, depending on the properties of the drug being produced.

V-Blender

The v-blender is used in almost all granulation processes to mix lubricants and the powdered drug. These blenders are made of two cylinders attached at an angle, mounted to an external frame. As the blender begins to tumble the material randomly mixes, which causes the final blend to be very homogeneous. For this reason these blenders are preferred in the pharmaceutical industry to ensure that each tablet or pill made is the same as all the others.

vblend.JPG

(Copyright Aadvanced Machinery Inc., Clinton Township, MI)

Cone Mill

Cone mills are the most widely used granulation equipment in the dry product process because they can perform both dry and wet milling depending on type of granulation required. Material is fed from a previous machine by gravity into the mill. As the material enters the conical chamber it is forced to the wall due to the force from the spinning rotor. The rotor blades exerts a shear stress on the material, which causes reduction in granule size. The granules then pass through the holes on the conical chambers walls when they reach a small enough size and fall into a container.

cmill.JPG

(Copyright Mendel Company, East Hanover, NJ)

Sieve

A sieve is a type of centrifugal screener used in all granulation processes to remove large particles from the bulk powder that could be problematic in the later process. Most pharmaceutical sieves have circular housings with an attached steel mesh, with size openings depending on the needs of the process. The housing is then vibrated to allow particles to pass through the mesh to the next part of the process.

sieve2.JPG

(Copyright Chemical Engineering, Access Intelligence, LLC)

Roller Compactor

The roller compactor is only used in dry granulation to compact the lubricated powder to produce the granules. The material is fed through a chute to two compacting wheels that compress the material into thin flakes. The material then exits to the dry mill to produce the granules.

rotcomp.JPG

(Copyright Fitzpatrick, Elmhurst, IL)

Mixer Granulator

A mixer granulator is used in wet granulation to combine the powder mixing, wetting, wet massing, and cutting operations of the granulation process. In powder mixing an impeller and chopper first rotate at high speeds to break up any clumps in the powder, then a liquid solution that binds the powder is charged to the system by pumping, spraying, or pouring. The impeller and chopper is then switched to a low speed for about two minutes to evenly mix the solution into the powder. Then the machine is switched back to high speed and runs for two minutes to increase the size of the granules. The material is then discharged to the next step in the process. The mixing granulator may be equipped with a heating or cooling jacket to achieve a desired temperature. The main bowl of the machine may also be on a pivot for more effective heat exchange.

mixgran.JPG

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

Fluid Bed Dryer

A fluid bed dryer is used in the wet granulation process to dry the material that comes from the mixer granulator and wet mill. Similar to the bulk product drying process air is filtered and circulated through the bed of material.

fbd.JPG

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

Spray Dryer

A spray dryer is used in the spray granulation process, which is only used when the materials are all soluble in a common solvent. Inside the dryer a gas is fed co-currently or counter-currently over the feed stream, evaporating the solvent. The solids are then separated from the gas stream by filters. The resulting particles are uniform and can be fed to the next process.

spray.JPG

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

Acknowledgements

Aadvanced Machinery Inc. , Clinton Township, MI

Chemical Engineering, Access Intelligence, LLC

Fitzpatrick , Elmhurst, IL

GEA Process Engineering Inc. , Columbia, MD

Mendel Company , East Hanover, NJ

References

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

Cone Mills. Bristol, PA: Kemutec. Web. kemutecusa.com.

O'Connell, Rob. "Sieve Use in the Pharmaceutical Industry." PharmTech. UBM Advanstar, 1 May 2005. Web.www.pharmtech.com

Roller Compactors for Dry Granulation. Germany: Powtec, n.d. Powtec. Powtec. Web. www.powtec.de.

Tekchandaney, Jayesh. "V-Blenders." Bright Hub Engineering. Bright Hub, Inc., 23 Oct. 2009. Web. www.brighthubengineering.com.

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