Accurate and reliable measurement of tablet detachment and ejection forces using Gamlen Tablet Press

by Michael Gamlen and Dipankar Dey at Gamlen Tableting Limited

The effect of lubricant concentration on tabletability, tablet ejection and detachment can be evaluated using the Gamlen Tablet Press. Lubricant effectiveness rank order varies between materials; some materials are better lubricated by sodium stearyl fumarate than by magnesium stearate.

Detachment (take-off) force and peak ejection force should be evaluated as potential critical quality attribute for tablets.

Introduction

Successful implementation of the principles of Quality by Design relies upon the capability to make accurate and reliable measurements of material properties. The critical quality attributes (CQAs) relating to tablet compression are tabletability, compressibility and compactibility. The CQAs relating to tablet lubrication are the ejection profile (peak ejection force and ejection force vs displacement profile), and the punch detachment, or take-off, force (force required to detach the tablet from the punch). In principle these should be optimised on a product by product basis.

Ejection studies on instrumented tablet machines are normally difficult to perform because the same load cell is used for measuring compression force as is used for ejection, but ejection forces are much smaller and so hard to measure accurately. Measurement of detachment, or punch take-off force is not normally undertaken at all during laboratory evaluation.

The purpose of this work was to study the impact of blending time and lubricant concentration on ejection and detachment as a trial for QbD lubrication studies.

Materials and methods

Galen IQ720®, Perlitol 500DC®, magnesium stearate (MS) and sodium stearyl fumarate (SSF, PRUV®) were used as received. Batches of 100g excipient were blended with 0.5 and 1% of each lubricant for 5min a Turbula blender. Tablets were compressed using the Gamlen Tablet Press GTP-1, at forces between 100 and 500kg using a 5mm punch and die and 70mg nominal tablet weight. Compaction and ejection forces, and punch displacement, are recorded by the machine automatically and exported to Excel for data analysis. The tablet detachment (take-off) force was recorded using a manually operated 500N McMesin CFG+ force transducer. Tablets were fractured at a speed of 1mm/min.

Data handling

Compaction pressures were calculated from the measured peak compaction force and the tablet cross sectional area. Ejection stress was calculated from the area of the tablet in contact with die at the point of ejection (assumed to be the cylindrical surface of the tablet). Detachment stress was calculated from the measured peak detachment force divided by the area of the tablet in contact with the punch. Tablet fracture stresses (TFS) were calculated from the tablet breaking load using the formula of Fell and Newton (1971):

formula

 

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Tablet in Die

 

 

 

 

 

 

 

 

 

 

 

 

Tabletability

The TFS of lubricated Pearlitol 500DCÒ was significantly higher than that of the unlubricated material.
See figure 1.

Unlubricated Galen IQ720 could not be ejected on the press. See figure 2

The impact of the lubricants on TFS was broadly similar, with only a small effects observed.

 

Figure 1 Tabletability Pearlitol 500 and Galen IQ720 with PRUV and MS

 

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Figure 2 Galen IQ720 Ejection stresses

Lubrication study results

Ejection and detachment stresses ranged between 2 and 12MPa. This compares with a proposed ejection stress limit of 5MPa which has been proposed as an upper limit for acceptable ejection stress on a manufacturing scale.

MS was a substantially better lubricant than SSF for Galen IQ720Ò with lower detachment and ejection forces under most conditions. The take-off stresses were higher than the ejection stresses under most conditions, except at low compaction pressures. In general, stresses increased with compaction pressure, with substantial detachment stresses for SSF at a concentration of 0.5%.

SSF generated lower ejection forces for Perlitol 500DC® than MS under most conditions, but the detachment forces for SSF were higher than for MS. The detachment stress for 0.5% magnesium stearate was much higher than the ejection stress under the same conditions. The impact of compaction pressure on ejection and detachment stresses was less than was seen for Galen IQ720Ò. In general, ejection and detachment stresses increased with compaction pressure.

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Figure 3 Galen IQ720 detachment stresses

 

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Figure 4 Pearlitol ejection stresses

 

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Figure 5 Pearlitol detachment stresses

 

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Why use a Gamlen Tablet Press?

It can save you time, money and materials. People need help to study tablets under properly controlled conditions in a laboratory.

Michael Gamlen invented the Gamlen Tablet Press (GTP) to help you understand the relationship between the properties of your drug, formulation, and manufacturing process. When you do this you can develop better products more quickly, and improve productivity of your tablet manufacturing operations.

The GTP is the first machine designed to make tablets on a small scale at a user-specified compaction force. This force determines both the physical strength and the dissolution behaviour of the tablet. These are the key properties which ensure the tablet reaches the patient and delivers the drug.

The machine works by monitoring the force in real time using a PLC.  The punch force and punch position are displayed in real time on a computer which is also used to input the compaction conditions. Using the GTP we make tablets of extraordinary reproducibility and consistency, within 1-2% force, and with no wastage. Batch yields are >99%.

For the measurement of tablet breaking load, the press records both force and displacement during both compression and fracture, and also provides the ejection force profile associated with tablet ejection

In the scale-up of tablet production, the press can be used to determine the relationship between tablets developed at the bench-top scale using a few grams of material (often at the early development stage) and the final tablet manufactured on a rotary tablet press. The latter uses hundreds of kilograms of material, making process development difficult because of practical difficulties in experimentation; smaller and different shaped tablets can, however, be scaled to the final desired tablet design if TFS is used as the basis for comparison.

If you want better tablet products and processes you need the Gamlen Tablet Press.

Conclusion

The effect of lubricant concentration on tabletability, tablet ejection and detachment can be evaluated using the Gamlen Tablet Press. Lubricant effectiveness rank order varies between materials; some materials are better lubricated by sodium stearyl fumarate than by magnesium stearate.

Detachment (take-off) force and peak ejection force should be evaluated as potential Critical Quality Attribute for tablets.

Reference

Fell and Newton J Pharm Pharmacol 20 657-658 (1968)

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