Compressing Force: Myth vs Reality

Compressing force is a dynamic number recorded as the attempt to maintain two target values in close tolerance

By Fred A. Rowley, Solid Dosage Training, Inc.

While recently reading several technical papers, one of which concerned itself with the effect of excipients, compressing force, film coating and storage on hypromelose performance, [1] it became apparent that there are many misconceptions on how a tablet press works. These papers specifically used the term compressing force, a term I find frequently misunderstood in technical conversation, both in academia and in industry. For example, during a recent discussion with several quality engineers, I heard each of them say that “during a compression run, the computer alters the compressing force to maintain tablet attributes.” This paper will explain what compressing force is and why the term is misused and misunderstood, so that future scientists can better understand and convey important data when compressing tablets. [2, 3, 4]

The reader may be shocked to learn that the list of scientific papers, articles and conversations that use compressing force and other conflicting solid dosage terms and references is almost endless. A recent question posed by a professional in the Journal of Validation Technology concerning compressing force, proves my point:

“The process validation of tablet compression processes is accomplished by testing quality attributes such as content uniformity, dissolution, moisture and other attributes from stratified sampling conducted throughout the process. Machine operating parameters may vary between lots; example parameters include precompressing force, main compressing force and turret speed. After appropriate set-up of operating parameters, in-process testing or machine control of tablet weight, thickness and hardness maintains compressing at target attributes by adjusting machine parameters.

“Question: How are ranges of operating parameters such as compressing forces and turret speeds handled in process validation? Are separate runs at high- and low-parameter extremes conducted to validate ranges of parameters? Or are multiple runs at the same parameter settings conducted to demonstrate repeatability? Any other options?” [5]

How can something as elementary as the force necessary to make a tablet be so misunderstood and misquoted? Many authors write about it, scientists wonder about it and manufacturing and quality units debate it. Unfortunately, even the professionals need to read the literature more closely to more fully understand what the various workers are trying to convey. [6]

Several decades ago, the term “compressing force” or “compression force” was not widely used. The terms “support pressure” or “tonnage” appeared far more frequently. At that time, tablet presses were less complex and these terms were easier to visualize and comprehend, since there wasn’t all that much to see. The primary press controls were both easy to see and understand.

In the 1970s, most presses had identical controls: thickness, pressure and hardness, all on the same labels. These were the only primary controls on the tablet presses of that era. There never was a “compressing force” control.

In addition, there was a spring-based device that set the maximum pressure each set of tooling tips could withstand. Infrequently, these pressure limiting devices had a gauge displaying what overload (pressure release) point had been set. On older presses, this was accomplished by compressing a spring and setting it to a specific force value.

l first noticed confusion over these terms when Manesty introduced the Rotopress and Mark II machines in the 1970s. These and other more advanced machines had a new gauge that was somewhere on the front control panel. It was frequently misread as “compressing force” and sometimes reported in the literature as such.

Where the disconnect between terms and actions may have come about was in the impression that somehow the force seen on that control panel dial was the force being used to manufacture tablets. [7] This was never the case. Other manufacturers, such as Kilian, Stokes and Fette also followed with different dials indicating pressure.

So why all of this confusion? Is compressing force real? What does it mean? Let us review the basic tablet press, the tablet compressing cycle and then discuss why this term requires clear understanding.

The Basic Tablet Compressing Cycle
As shown in the figure 1, going from left to right, powder is fed into the horizontal feeder from the powder hopper. [8] The powder floods a portion of the die table and then enters the die. The desired fill volume, called tablet weight, is adjusted with the first control, called the weight cam.

After the excess powder has been scraped off, the powder in the die is pressed together by the action of the upper and lower punches rolling over the pressure rolls. The desired tablet thickness is obtained by moving the lower pressure roll either away from or closer to the fixed upper pressure roll. Doing this moves the lower punches either away from or closer to the upper punches. This is tablet thickness.

Other than press speed, on many tablet presses these are the only controls (also called adjustments or set points) available to the operator. There is no “compressing force” control and many presses do not have any means to read this value.

On more advanced tablet presses, there are several second-tier controls called the pre-compression station, the upper-punch entry adjustment, the powder feeder speed and the pre-compressing tablet thickness control. None of these have any direct impact on what we call compressing force. Even on computer-adjusted tablet presses used today, there is no control named “compressing force.” There are three basic controls: press speed, die-fill volume (weight) and the distance between the punch tips (expressed as tablet thickness).

The research paper mentioned earlier contained a table showing “the influence of compression force and fillers on drug release (T50%) from HPMC SR tablets” which included a section listing values of “(T50%) for tablets manufactured at different compression forces (4kN, 10kN and 14kN).” How is it possible that one can list three different compression forces using a constant set of excipients at “different compressing forces”? In addition, on a basic tablet press, where would one make such an adjustment to achieve the forces of 4kN, 10kN and 14kN?

The answer is that we will need to use one or both of the two primary controls available to us: weight (fill) and thickness (distance between the punches) to achieve these three compressing force values. Doing this becomes even more difficult when manufacturing commercial pharmaceutical tablets, as we are mandated to try to achieve and hold a specific target weight [9, 10]. Raising or lowering of the weight cam may only be made when the weight moves off of target. This leaves us with only the thickness adjustment, keeping the weight constant, or a combination of thickness and weight adjustments to maintain a specific “compressing force” set point. Since the compressing cycle is a dynamic process, with fill volumes (weights) changing slightly from station to station in any one turret rotation, the actual compressing force varies slightly in this dynamic system.

Compressing force is an artifact or function of a combination of any set of unique fill volumes (weight) and thickness values that one might choose for any particular active ingredient and tablet size/shape [9, 10]. In many cases, varying either the fill volume or thickness and you will vary the compressing force necessary to make that tablet. Presses having digital readouts for compressing force will display a constantly changing number, however slight, with slight changes of powder mix or uniformity of the mix density. Therefore, the numbers reported in the tables and reports that one reads in scientific literature are actually approximate descriptions of what was going on. Further, if the fill volumes were held constant at slow speed, they are describing changes made in tablet thickness. Conversely, if the thickness control was left untouched, they are describing slight changes in fill volume.

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Different active ingredients require different levels of force to compress a tablet, even into a tablet of the same shape. Different quantities of the same active ingredient may also require different settings for the same tablet shape. [11] There is no single universal number except for the maximum force that the punch tips can withstand before they fracture, and this number is not related to compressing force.

What Compressing Force Is and Is Not
After achieving our target fill volume (weight) and thickness, we may then convey these targets to the computer and measure the compressing force required to maintain these conditions. On modern tablet presses, these readings are taken using a device that measures the effect of the force on an elastic element, called a load cell. [12] The term load cell is used to describe a transducer that generates a voltage signal as a result of an applied force, usually along a particular direction. [13] With electric load cells, that effect is a deformation or a displacement. Some systems use hydraulic or pneumatic load cells, where increases in pressure of a liquid or gas are used.

When a mechanical force is applied to a nonmobile elastic element, it strains until the strain-generated stresses balance those due to the applied force. [14] This is called “support pressure.” Under normal compressing settings, the spring does not move, but when the support value is exceeded, the lower pressure roll separates. Thus, the instrument registers a simple measurement of

Fig 1. An illustration of the tablet compressing cycle and the two basic controls available on the rotary tablet press.

distance that is linearly related to force within the elastic range of the spring. [15] Typically, a tablet press can use two types of measuring devices: force control or displacement control.

The force control principle is based on the measurement of final compression force with the tablet thickness held or considered constant. If the powder characteristics change in a system using force control, the control system has to be corrected to bring the average tablet weight back to the target value. Since most powder blends tend to slightly segregate as they transit from the tote bin or drum through the feeder and into the die, slight differences in both fill volume (tablet weight) and thickness may be expected and require correction. This correction is the re-calibration of the primary control loop, performed by changing either the target values of the compression force and/or the main compression height (tablet thickness) of the tablet press. In both cases, hardness may also be affected.

Displacement control is accomplished by making fine adjustments based on the displacement of the pressure roll. This technology appears primarily in Courtoy presses (Belgium) and is equally effective. [16]

It is almost impossible to understate the importance of the concept that the relationship between tablet thickness and hardness is not (in most cases) a direct 1:1 ratio. In some formulas, you have to significantly decrease the tablet thickness before you will see a corresponding measurable response in tablet hardness. In other formulas, even a minor decrease in tablet thickness will bring an immediate increase response in tablet hardness. Karnavati America, a vendor in the area of monitoring tablet presses using strain gauges, explains:

  • Every product under compression behaves peculiarly.
  • “Tablet thickness is inversely proportional to compression force” may not be true always.
  • “Tablet friability is inversely proportional to tablet thickness” may not be true always. [11]

And what would one see if one measured compression force during the transition from a thicker to thinner tablet in each of these two examples? In the first case, compression force would immediately increase and would continue to climb, forming a somewhat scattered cluster of the three values. In the second case, because the hardness goal was quickly achieved, the observer would notice little change in compressing force, forming a tight cluster of the three values.

So while compressing force is the force necessary to make a tablet, it is a function of different combinations of fill volumes and thickness targets and may vary; sometimes dramatically, when slight adjustments are made to either the fill volume or thickness controls.

With some computer-controlled tablet presses, it is possible to save a particular set of conditions used to manufacture a product. In this case, the press will adjust the positions of the weight cam, thickness control and press speed to those last used to successfully make the product. However, it does not recall compressing force and does not directly set “compressing force” during this parameter recall. Even if it did, if either the press speed or powder-blend density subsequently changed, so would the resultant compressing force.

This is part of the myth about compressing force; that somehow the computer-controlled press resets the exact compressing force. That is not true; there is no such control to adjust. Even with advanced dual-control systems, like the GEA Niro “Dual Weight Hardness Control System,” the system still adjusts tablet weight and tablet thickness using a derivative calculation. [17]

Finally, what do those compressing forces cited actually mean? Theoretically, they may represent more than one set of operational conditions:

  1. Three different thickness settings with the fill volume being held constant. While not stated, the thickness settings may be either very close to each other or dramatically different, depending on the level of the binder used, the nature and quantity of the active ingredient(s) used to formulate the tablet and the various excipient loads.
  2. Three different tablet weights with the tablet thickness being held constant.
  3. Three different hardness targets with either tablet weight or tablet thickness (but not both) held constant.

Again, note that with the tablet weight constant, the thickness settings necessary to achieve the stated compressing forces may be closely clustered together or distinctly far apart, depending on the nature and quantity of the active ingredients in the tablet.

Summary

Compressing force is real but it is not a true machine set point. It is not a static number, almost always appearing as a set point when reported in the literature. It is a dynamic number recorded as the attempt to maintain two target values in close tolerance.

Change the weight, the thickness or both and you will have a corresponding change in the compressing force necessary to make the tablet.


References

  1. Levina, M., “Influence of Fillers, Compression Force, Film Coatings & Storage Conditions on Performance of Hypromellose Matrices,” Drug Delivery Technology.
  2. Ford, J.L., Rubinstein, M.H., McCaul, F., Hogan, J.E., Edgar, P.J., “Importance of drug type, tablet shape and added diluents on release kinetics from hydroxypropyl methylcellulose matrix tablets.” Int J Pharm. 1987; 40:233-234.
  3. Velasco, M.V., Ford, J.L., Rowe, P., Rajabi- Siahboomi, A.R, “Influence of drug: hydroxy propylmethylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC tablets.” J Contr Rel. 1999; 57:75-85.
  4. Doelker, E., “Water-soluble cellulose derivatives in pharmacy”. Peppas, N.A., ed. Hydrogels in Medicine and Pharmacy Volume II: Polymers. Boca Raton, FL, CRC Press, Inc., 1987.
  5. Journal of Validation Technology, posted November 13, 2006.
  6. Hite, M., Federice, C., London, C., Brunelle, A., Fassihi, R., “Scale-Up Operation of a Novel Monolithic Controlled Release Tablet Formulation.” SCOLR Pharma. www.Scolr.com
  7. Tousey, M., “Preventing and Fixing Weight and Hardness Defects: Strategies For Production Personnel,” Tablets & Capsules, (9), 34-38, 2004.
  8. Tousey, M., “Optimum Tablet Press Optimization: Machine Versus Granulation,” Pharm. Tech, (1), 2002.
  9. Thomas Engineering, Technical Bulletin, “Tablet Press Scale Up,” dated 5/24/2002.
  10. Borroto, A., “Determination of The Optimum Speed Regimen of Tablet Presses During Product Development,” Tablet & Capsules, 4(6), 2006.
  11. Karnavati America, web site. www.karnavati. com.
  12. Carstens, J., “Electrical Sensors and Transducers,” Prentice Hall, 1993, 29-31, 225.
  13. Dally, J.W., Riley, W.F., and McConnell, K.G., “Instrumentation for Engineering Measurements,” Wiley, 1993, 2nd Ed. 211-47, 252-90.
  14. Figiola, F., “Theory and Design for Mechanical Measurements,” Wiley, 1995, 2nd Ed., 391- 411, 560-70.
  15. Pallas-Areny, R., “Sensors and Signal Conditioning,” Wiley, 1991, 29-31, 171-2.
  16. Nachtigal, C.L., “Instrumentation and Control,” Wiley, 1990, 265-75, 402-34.
  17. GEA Niro Inc., website. www.Niroinc.com.

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