Multilayer-Tablet Technology - Pharmaceutical Technology

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PharmTech

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PharmTech Europe

Multilayer-Tablet Technology
Industry experts discuss formulation and technical challenges in multilayer tablet manufacture.


Pharmaceutical Technology
Volume 36, Issue 1, pp. 48-50

PharmTech: How can the weight of individual layers be monitored and controlled accurately?

Behrens (IMA): When producing bilayer tablets, the in-line control of production, combining compression force measurement and statistical weight check are challenging for several reasons. If the compaction force for layer one is extremely low, it could be difficult to obtain a clear signal from the strain gauges. Low-force compression rollers are available to help deal with this. The reduced mass ensures more accurate and reliable measurements. Another critical point is statistical sampling of the layers for weight checking. For sampling, the first layer has to be compressed at a higher force to achieve enough hardness to make sampling and weighing possible. Some systems can achieve this by using specialized systems. For example, to avoid the production of second-layer-only tablets during layer one sampling, lower punches can remain in the up position while the fill-shoe for layer two is stopped.

Calvin (Elizabeth): Usually, two different process-control methods are employed to achieve this. The first standard method is to utilize force control, which monitors the layer tamping pressure by means of a strain gauge transducer that, in turn, provides feedback to the press controller. This information is used to automatically adjust the metering cam to keep the set pressure constant to maintain the correct weight and tamping pressure. The strain gauge should be sized so that it will be sensitive enough to "sense" the lighter tamping pressures required for producing a tablet layer compared to the strain gauge that would be required for final tablet compression. The secondary method is to select a multilayer tablet press that automatically collects sample tablets from each layer at regular intervals and sends them to a weight testing unit, which would be included in the press control feedback loop, to provide in-process checks and weight control.

Kirsch (Natoli): Tablet press manufactures will be responsible for this through improved technology and engineering. By utilizing quality by design, the science of the formulation is understood and the design space can be exploited to deliver a controllable process. Controlled processes deliver a product with the required critical quality attributes that define what is to be delivered to the patient.

PharmTech: How can layer cross-contamination be avoided?

Behrens (IMA): Product losses can be very high when making layered tablets. Usually strong vacuum aspiration is used to clean the residual product on the die table after the dosage of each layer, thus preventing cross contamination. Over the years, vendors have developed several technical solutions that minimize the quantity of powder remaining on the die plate that needs to be removed by suction.

Calvin (Elizabeth): This can be avoided in a few ways. Ensuring the feed frame is correctly adjusted and not leaking powder, properly adjusting the vacuum being applied to the front of the feedframe to keep the die table clean, and installing dies that are manufactured to the high limit on overall die height. Whenever the granulation characteristics and tablet size deem it necessary, a "Tail Over Die Scraper" (a delrin cover that is held in place against the die table with spring steel to keep any granulation form slinging out of the die through centrifugal force) may be needed if any powder loss is incurred due to centrifugal force.

Kirsch (Natoli): Proper press setup is essential. Turret die tables have a certain amount of vertical run out. Often overlooked is the simple task of indicating a die table to locate the high point. Feeder clearance must be set at this point to achieve a minimal amount of clearance between the feeder and die table to reduce granulation loss. Scraper blades must be in good condition and free floating on the die table to reduce cross contamination. Die tables must also be in excellent condition as any wear or damage will contribute to granulation crossover. Proper dust extraction is also needed as presses suited for layered tablets generally have more and/or specifically designed vacuum nozzles. Skilled press setup technicians and operators are a must.

Ethirajan (Tedor): Scraper and seal conditions of the feed frames are very important. It is also essential that excess granulation passing the scrape-off be vacuum cleaned so that fines from one layer don't cross contaminate the other. Reduced fill cams may be used to reduce the amount of granulation that needs to be scraped off from overfill of the die.


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