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This article examines multi-tip tool technology for pharmaceutical tablet compression and the process control and validation issues that must be carefully evaluated to assess the potential for success.
The prospect of using multi-tip tools to increase production output on a single tablet press has long been considered by process engineers who seek additional capacity with minimal capital investment. The math is simple: a press tool design with two or three tips will produce two or three times the output of a press running with single-tip tools. There are technical and validation challenges, however, that are often difficult to navigate. This article examines multi-tip tool technology and the process control and validation issues that must be carefully evaluated to assess the potential for success.
Rotary tablet presses are configured with press tools consisting of an upper punch, lower punch, and die. For most applications, the upper punch has a single tip, which is configured to match the geometry of the tablet being produced. Tablet press tooling geometry is governed by the US standard in the American Pharmacists Association’s Tableting Specification Manual (TSM) (1) and the European Euronorm standard (2). These standards define the tooling length, tool head geometry, and related tolerances. Most modern tablet presses offer an exchangeable turret capability that permit tablets of different sizes (using different tool standards) to be produced on the same press. Table I lists typical turret configurations for a single and double-sided press.
For all tablet press designs, the pitch circle of the die table for a given press is fixed, and the number of punches is different to meet varying tooling standards; this set-up allows, for example, an increased number of punch stations when the die size is smaller. For a single-sided tablet press, which produces one tablet per revolution, at any given press speed, the output is calculated by Equation 1:
Output (tablets/hour) = Press speed (revolutions/min) x Number of punch stations x 60 min/h. [Eq. 1]
Many customers leverage exchangeable turret technology to maximize output based on tablet size. For example, for an 8-mm tablet running on a standard 35-station B turret at 80 RPM, the output is calculated as follows using Equation 1:
Output = 80 rev/min x 35 x 60 min/hour = 168,000 tablets/h.
For the same tablet on a 47-station BBS turret at the same press speed, the output would be:
Output = 80 rev/min x 47 x 60 min/hour = 225,600 tablets/h.
The use of the BBS turret, with identical processing parameters including press speed, compression dwell time, and feeder dwell time, has resulted in an output improvement of 34.3%.
For double-sided rotary presses, which produce two tablets per revolution and are designed for high volume production, the number of punch stations and nominal turret sizes are listed in Table I.
At any given press speed, the output is then calculated using Equation 2:
Output (tablets/hour) = Press speed (rev/min) x Number of punch stations x 2 x 60 min/h. [Eq. 2]
For the same 8-mm tablet running on a standard 71-station B turret at 60 RPM, the output is calculated as follows:
Output = 60 rev/min x 71 x 2 X 60 min/h = 511,200 tablets/h.
For the same tablet on a 95-station BBS turret at the same press speed, the output becomes:
Output = 60 rev/min x 95 x 2 x 60 min/h = 684,000 tablets/h.
The use of the BBS turret, with identical processing parameters including press speed, compression dwell time, and feeder dwell time, has resulted in an output improvement of 33.8%.
Running a product on a turret that maximizes production output is an excellent strategy for maximizing tablet compression capacity. However, whenever a significant increase in tablet production capacity is required, the issue of multi-tip tools (see Figure 1, for example) is often at the center of the discussion.
Based on the tablet size and tool specification, it is often possible to configure the upper and lower punches with multiple tips that will compress and eject multiple tablets at each punch station. In theory, the use of multi-tip tools can dramatically increase production capacity by the multiple of the tips that can fit on the press tool. In general, the number of tips that can be incorporated on a single punch is a function of the tablet size and the turret being utilized, as listed in Table II.
Returning to the example of the 8-mm tablet, using a 5-tip tool configuration on the 59-station turret would achieve an output as follows:
Output = 60 rev/min x 59 x 5 x 60 min/h = 1,062,000 tablets/h.
This represents an improvement of 107% of the nominal output achieved with single-tip tools on the 71-station B turret, and an improvement of 55% over the nominal output achieved with the 95-station BBS turret. This appears to be an easy decision for a good return on investment (ROI), as outputs can be doubled and only a single set of multi-tip tools is required. Unfortunately, there are constraints and challenges that make this seemingly simple calculation complicated to implement. Understanding these constraints requires a fundamental understanding of press force control theory and tablet rejection systems on modern tablet presses.
Tablet weight is the critical quality attribute for virtually all tablet compression applications. Precision tablet weight control ensures that each tablet delivers the prescribed dosage of active ingredient. Even with the most advanced tablet testing technology, tablet presses can still produce tablets faster than the tablet weight can be measured. Periodic samples and statistical control methods are fine, and there is a secondary parameter-the press force required to produce each tablet-that can be measured in real-time as the basis for automatic tablet weight control. This system permits the real-time, in-process measurement of tablet weight and the ability to reject individual tablets that exceed indicated quality control limits.
In general, press force control theory can be explained as follows:
Along with a high-speed encoder, press force instrumentation, which is generally mounted on the compression roller shaft, permits the peak compression force of each tablet to be measured. This allows the real-time inspection of each and every tablet that is produced. Once the tablet press has been set up to achieve the specified tablet weight, thickness, and hardness, the resulting press force is measured and established as the press force setpoint. To set up press force limits, the tablet weight is adjusted to the high average limit, and the resulting compression force is then established as the high average limit. For the high single-value press force limit, the tablet weight is adjusted once again to the maximum individual tablet weight, and the resulting compression force is then established as the upper reject limit. The same procedure is then utilized to establish the lower average and lower reject limit.
The press force control loop will then measure the press force associated with each and every tablet produced. An average force will be calculated (usually using a moving average algorithm) and compared to the press force setpoint. A low average compression force would indicate that the weight is slightly low, and the tablet press makes a closed loop correction to the dosing cam to increase the amount of material in the dies. A high average force would indicate that weight is slightly high, and the tablet press makes a closed loop correction to the dosing cam to decrease the amount of material in the dies. The adjustments are very precise and configured such that the system is tuned to return to the desired press force without hunting or overshooting the adjustment. If the average compression force violates the upper and lower limits, then the press is stopped instantaneously. This general press force control algorithm has been in use for more than 30 years.
The measurement of individual press forces permits the detection of out-of-spec tablets, which present as a high or low force and which violate the upper and lower tablet rejection limits of the force control system. Most modern rotary tablet presses offer a single-tablet rejection system, which will reliably remove a single tablet from the product stream. A mechanical gate, or more commonly, a very short burst of compressed air, will remove an individual tablet across the full operating speed range of the machine.
The key constraint in the use of multi-tip tooling is the validation question pertaining to press force measurement and the ability to reject individual tablets that may be out of specification. Press force control theory, which matches an individual press force measurement to a corresponding tablet weight, encounters significant challenges when multi-tip tools are used. In essence, multiple tablets are being produced, but only a single force is being measured.
In theory, a press force associated with multiple perfect tablets may be the same as the press force associated with a combination of overweight and underweight tablets. As such, the use of multi-tip tools does not permit the measurement of the individual press force for each tablet, which eliminates the ability to reject individual tablets. In most cases, this limitation is enough to derail any consideration of the use of multi-tip tools.
There are also additional process constraints that must be considered. When a punch is configured with multiple tips, the force exerted by the head of the punch on the compression roller is cumulative. That is, if one 8-mm tablet requires a 10 kN compression force, then a press tool with 5 tips will measure 50 kN. In general, products that required higher compression forces will run at a slower press speed than products that require low compression forces. Indeed, in many cases, whatever output gain may be realized with multi-tip tools is quickly offset by the speed reduction associated with the comparably high cumulative compression force requirement.
There is also the matter of die fill. Producing a single, 8-mm tablet of a specific tablet weight will permit a higher press speed than a process where it is necessary to fill five die holes for every punch station. For products that have less than robust flow properties, again, any output gain associated with multi-tip tooling can be offset by the speed reduction required to achieve consistent die fill.
Multi-tip tools are best when the tablet weight control is not critical. Outside of the pharmaceutical industry, for example, producing small mints and sweeteners at rates that exceed 1,000,000 tablets per hour is quite common with the use of multi-tip tooling.
For those who seek to utilize multi-tip tools for pharmaceutical and nutraceutical products, the only way to overcome the press force control/tablet rejection validation constraint is to develop a statistical case that demonstrates consistent and superior process capability-one in which all tablets are well within the specification limits at all times. This requires the calculation of process capability for tablet weight, thickness, and hardness, as described in Equation 3.
Cp = (USL – LSL) / 6 X Σ [Eq. 3]
where Cp = process capability index, USL = upper specification limit, LSL = lower specification limit, and Σ = standard deviation.
The process capability index is the ratio of the upper and lower specification limit, divided by six sigma, which comprehends 99.7% of the process samples, as shown in Figure 2. A process capability index of 1.67 or higher is generally considered to be good, but the final determination is a question for the quality control group. In general, the process capability index must be evaluated for all critical process quality attributes, including tablet weight, thickness, hardness, dissolution, and content uniformity.
The use of multi-tip tools does seem to present a compelling opportunity to significantly increase production output on a tablet press. However, critical and technically valid constraints surrounding product quality and process validation have significantly limited the application of this technology in pharmaceutical manufacturing. The inability to reject an individual tablet, or even to recognize a high or lower individual force associated with a tablet reject, remains the key barrier.
For small tablet formats with low compression forces and superior material flow properties, including mini-tablets, it is possible to leverage the use of multi-tip tools based on a substantial statistical analysis of process capability in the context of specification limits. For larger tablets and higher compression forces, any potential gain with multi-tip tools is usually offset by the need to slow the machine down based on the cumulative press force, and/or the dwell time required to fill multiple die holes on each station. And again, the inability to reject an individual tablet, or even to recognize a high or lower individual force associated with a tablet reject, remains the primary obstacle to successful implementation.
Multi-tip tooling does offer an opportunity for significant capacity increases. However, the high-cost of multi-tip tools as compared to conventional, single-tips must be considered in determining the true ROI.
1. American Pharmacists Association, Tableting Specification Manual, 7th Edition (Washington, DC, 2006).
2. ISO, ISO 18084:2011, Press Tools for Tablets-Punches and Dies (2011).
Frederick Murray is president of KORSCH America Inc., email@example.com.
Supplement: Solid Dosage Drug Development and Manufacturing
When referring to this article, please cite it as F. Murray, “Considerations for Tablet Compression with Multi-Tip Tooling,” Solid Dosage Drug Development and Manufacturing Supplement (April 2020).