Multilayer Tablets: Key Challenges and Trends - Pharmaceutical Technology

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Multilayer Tablets: Key Challenges and Trends
Experts in solid dosage discuss the formulation and manufacture of multilayer tablets.

Pharmaceutical Technology
Volume 36, Issue 3, pp. s22-s33

Control

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

Behrens (IMA Kilian): 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 very 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 Companies): 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 then sends them to a weight testing unit, which would be included in the press control feedback loop, to provide in-process checks along with weight control.

Kirsch (Natoli): Tablet press manufacturers 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.

Aesthetics

PharmTech: Aesthetically, what consideration should be given to color?

Kirsch (Natoli): Aesthetics are always important to the consumer. However, as a manufacturer, the first concern would be, what the cost is and how well does it compress? Colors as well as flavors can affect tablet compression. Some may be more heat sensitive than others, resulting in picking or sticking issues. Others may have excessive fines resulting in punch and die binding, which increases tool and press wear.

A common error is developing a new product in R&D on a slow, partially tooled press and then submitting a New Drug Application before testing it on a production machine. The R&D press may not even have the same type tooling. If the product was developed on a 'D' tooling press and the production press was a 'B', dwell time would be reduced, resulting in poor layer cohesion or soft tablets. Partial sets of tooling will result in more time under pressure, therefore increasing tablet hardness. Again, poor layer cohesion and soft tablets could be an issue on a high-speed press. Production presses run at higher speeds and temperatures, increasing possible sticking, picking, laminating, and capping issues.

The criteria for color or flavor choice should be what is least costly and runs best on a production press and not just what 'looks pretty.' There is a middle ground somewhere for marketing and production. Marketing will not have to deal with the production headaches. It may cost thousands or hundreds of thousands to do a trial on a production press, but would be more cost effective than wasting millions fighting it in full-scale production.

Ethirajan (Tedor Pharma): Colors play an important role in multilayered tablets. Firstly, it is a method of visual process control during compression. The extent of cross contamination, if any, can be easily seen when granulations of different colors are mixed during compression. When a color coating is not present, colored tablets also give a visual description to the drug product. In the case of over-the-counter products, color and aesthetics play a major role in consumer choice.


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