Dwelling on it —how does dwell time impact tablet manufacturing?

In an environment where production speed is becoming more important and efficiency while being economical is a driver for manufacturers, acknowledging the significance of dwell time in tablet production is a must. Here, I Holland details how dwell time impacts tablet manufacturing and reveals the new technology that may help with the production process. 

Many tablet formulations are dwell-sensitive and require more time under compression to ensure they come off the press without any faults. In tablet compression, dwell time is the time that the punch head remains in contact with the compression roller. It is defined as the amount of time that the compression force applied when forming the tablet is above 90% of its peak value.

Some granules are extremely difficult to compress effectively and require extended time under peak compression to obtain the required tablet hardness and prevent any difficulties like sticking, one of the most frequent and challenging problems in tablet manufacture. Sticking is the build-up of granule on the punch tip face, this leads to tablet press downtime and reduced tablet output. Quite often to solve the problem, the press speed is reduced or a higher compression force is applied. Both these solutions can solve a sticking issue but can also cause other issues such as lower productivity and a longer dissolution time due to the increased tablet hardness.

It is not just sticking that can cause production problems, capping and delamination may also be an issue. Trapped air pockets in the forming tablet can cause severe problems during manufacture. If the air is insufficiently squeezed out and/or density variations occur in the tablet volume, the tablet tensile strength is negatively affected and the risk of tablet capping or delamination increases.

One of the most effective methods to reduce the risk of air entrapment is to extend the dwell time to expel air from the tablet, alternatively tapered dies can be used or the press can be slowed down but this again has a negative effect on production rates.

Do you know your formulations characteristics?

If problems like sticking or capping do occur, consideration must also be given to the characteristic of the ingredients within a formulation. They can feature plastic or elastic properties, which play an important role in the compaction of a tablet as they influence the contact between particles.

Particles that display elastic form will change shape during applied stress, however this is reversible, with the particle returning back to its original shape when the applied stress is alleviated. Plastic properties on the other hand display very different characteristics. When stress is applied they are permanently deformed. Their behaviours can change depending on the force employed and the length of time beneath it. In formulations that have more time-dependent consolidation behaviour, a long dwell time is important to create strong bonds between the particles and form a solid dose that does not result in problems like capping.

A formulation may also have non-cohesive characteristics where particles fail to bind together adequately resulting in friability with tablets having the tendency to crack, chip or break during compression. By analysing key production factors including dwell time, weight control, expansion and the tooling condition, the possibility and impact of friability can be minimised to produce a quality tablet.

Moisture within a tablet also plays an important role within dwell time. When the adhesive forces of the formulation to the punch tips overcome the cohesive forces within the tablet then sticking can occur.

Water can be one of the causes of a rise in adhesive forces; this happens by the increase in capillary action between the tooling surface and the granule. Capillary bridges form causing high adhesion areas, and so initiating sticking. Moisture can enter into the process either in wet granulation or due to excess humidity in the compression chamber of a non-environmentally controlled area; the latter can even impact direct compression formulations.

To form effective tablets from granulate, significant compression force is required, however, the exact amount of force and period of time that is applied needs to be carefully calculated. Too much or too little of either can result in irreversible tabletting or tooling issues during production.

If dwell time is significant then the area of punch head flat available can be a major factor in determining the overall success and profitability of tablet production. In a situation whereby a greater compression period is required there are tools on the market to help. Extended dwell flat tooling, which uses an elliptical head form to lengthen dwell time, enables a suitable compression dwell time for a formulation without the disadvantage of slowing the press.

I Holland has developed an innovative tool to do this, the eXtended Dwell Flat (XDF). By using XDF, turrets and cams do not have to be modified, unlike other tooling and equipment used to increase dwell and the press speed does not have to be reduced. For XDF tooling both the upper and lower punches are required to travel under the compression roller in the correct orientation to extend the dwell time. With punches used to manufacture a shaped tablet, the punches are already held in the correct orientation so no further change of specification is need to run XDF tools. When round tablets are being manufactured, anti-turn keys are added to the tooling to keep the tool in the correct orientation (just like it would be for shaped tooling).

It has been proven that extended dwell flat tooling can have a huge impact on tablet output, for example a press with a Pitch Circle Diameter (PCD) of 450 mm with Euro ‘B’ tooling (9.5 mm head flat) compared to XDF tooling (15 mm dwell flat) would have the following dwell times when the press is run at increasing RPMs.

The use of XDF tooling increases tablet output (tablets per hour — tph) by nearly 60% on the same dwell time as an Euro ‘B’.

Extensive studies have taken place to look at the benefits of XDF tooling when compared to other dwell time increasing options. The tests showed that XDF tooling outperformed competitors tooling when compressing tablets from difficult to compress formulation, for example plastic or elastic forms.

In a recent study for a difficult to compress elastic formulation (approx. 90% starch), the tensile strength of the tablet increased significantly over the standard tooling with increasing compression forces.

CASE STUDY

These results were proven in a production environment. A leading pharmaceutical manufacturer had been experiencing problems with tablet friability when running the press at high speeds.

The customer’s production expectations were as follows:

Run speed = 225k tph

Target tablet hardness = 8.5 kP

Tablet weight specification = 3.46–3.66 g

Friability (20 tablets for 30 mins at 25 rpm) = No tablet failures (capping or broken)

Using their existing Euro B tooling, the customer was able to run their tablet press at just 150k tph due to a variation in tablet hardness. It resulted in a reduced output of 75k tph against their target.

During these trials, it was identified that slowing the press seemed to eradicate the friability issues. It was this conclusion that led I Holland to recommend increasing the dwell time with XDF tooling. The elliptical head flat design fitted directly into their current tablet press and turret without costly changes to the machine and would potentially increase the dwell time by almost 60%.

In this case, as the press was running smoothly at 150k tph (with a standard head flat), using XDF tooling with an optimised head flat allowed production to be increased. The required speed of 225k tph was achieved using all the standard cam tracks and press equipment, presenting a significant cost saving.

The customer was able to produce excellent quality tablets to the correct hardness, friability and weight specifications at an optimum tablet press speed of 225k tph. This resulted in a 50% increase in tablet output and a significant time saving in production.

Following the trial, the customer independently performed a very comprehensive validation process, concluding that XDF tooling should always be used with this difficult formulation.

Overall it has been demonstrated through rigorous trials that the use of tooling like I Holland’s XDF helps to prevent problems like sticking, capping and friability. It also has the added benefit of being used to stop poor embossing definition and improve tablet hardness.

Summary

Dwell time plays a significant part in determining if a tablet can be produced successfully, especially those incorporating formulations that are challenging to compress.

Many tablet formulations are dwell sensitive and the time they are under compression has a huge impact on the final product. If a formulation displays difficult non-cohesive characteristics, for example, plastic or elastic properties, the amount of time the formulation is under compression has an impact on production, for example, stopping the press due to problems like sticking and capping.

By adding new technology, like extended flat head tooling, dwell time can be increased to form quality tablets and at an increased output. There is also the benefit of the tooling running on an existing table press without the need for time-consuming and expensive modifications.

With the increasing requirement to produce quality tablets quickly and efficiently in the most economical way possible, implementing tooling that will help in the production process is essential.