Rob Blanchard

The requirement for quality tablets to be produced quickly and cheaply have led to the advancements in tooling. To achieve problem-free tablet production, many processes must be investigated, and one of the main considerations to examine is the dwell time.

	Dwell time is defined as the amount of time each individual punch head flat is in contact with the compression roller of a rotary tablet press when the compression force applied to form the tablet is above 90% of its peak value.

	How formulation characteristics can have an impact on dwell time

	Many issues can be traced to the characteristics of certain ingredients in a formulation that display differing plastic or elastic properties. These plastic or elastic properties can lead to tableting issues such as sticking and capping. Particles that exhibit elastic form will change shape during applied stress; however, this effect is not completely permanent, with the particle returning to its original shape when the applied stress is alleviated. Those ingredients displaying plastic properties are permanently deformed when stress is applied above their elastic limit. The force employed and the length of time in compression can affect the way the formulation reacts, where the behavior of a particle under compression can either stay deformed or “spring back” to its original shape. In cases of formulations with more time dependent consolidation behavior, a long dwell time is important to create strong bonds between the particles.

	Punch displacement velocity (i.e., strain rate) and dwell time are two factors that can significantly affect the compression behavior of powders (1). As a rule of thumb, slower compression and decompression speeds and longer dwell times will improve the mechanical properties of a tablet (1). When certain elastic particles are subjected to a compression force for a longer period, further plastic behavior is demonstrated; less “spring back” happens, which results in a more stable compacted tablet.

	There may also be the problem of tablet friability with the tendency to crack, chip, or break during compression because of the formulation. It is important to get the compression force right-too high and it can adversely affect the tablet, but if the formulation is not cohesive and does not bind together sufficiently, then friability will occur. 

	Many tablet formulations are dwell sensitive and require more time under compression to guarantee that they come out of the press without any faults. Some granules are difficult to compress effectively and require extended time under peak compression to ensure they receive the required hardness to shape into the fully formed tablet.

	At pre-compression, a long dwell time at low to medium compression force is essential to expel air from the powderbed and for uniform distribution ofgranules in the die bore prior to finalcompaction under the main compression.Air must be expelled in order forthe particles to stick together and formthe tablet.

	Air in the formulation 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 (when the top of tablet separates horizontally when ejected from the press) or delamination (when the tablet splits apart) increases.

	The crucial importance of extended dwell time can be illustrated by the frequent application of other techniques to increase the time that the punch is in contact with the compression roller, for example: 

		Reduction of the tablet press speed in case of capping or insufficient hardness 

		Installation of larger compression rollers to increase the total compression time 

		Use of punches with a larger head to increase the size of the dwell flat. 

	These options are not always viable with the strict time and monetary constraints put on tablet manufacturers. This dwell time issue and customer demand led I Holland to investigate a method to increase the dwell time without slowing the press so that production could run sufficiently. 

	I Holland designed an elliptical head form, the eXtended dwell flat (XDF), to increase dwell time on existing presses without the need for expensive modifications. XDF can run on standard cams, giving users higher press speeds with challenging products and formulations. It also enhances tablet compaction/cohesion and can increase dwell time by up to 50% over a standard punch head, allowing more dwell than a D-type punch on a B-type tool. This increase helps to solve compression problems without upsizing punches or investing in a new press. 

	The following case study illustrates the benefits of XDF tooling in a production environment when tested by a leading pharmaceutical manufacturer. 

A specialty pharmaceutical company agreed to assess the XDF tooling. The goal was to create an operating environment where tablet quality was increased and waste reduction was improved on the production of a cold and flu tablet. The formulation would regularly stick to upper and lower punch faces. To minimize the problem, several methods were used to increase the compaction force, such as run the press to rejects to clear the sticking and manually scrape the tooling or remove the tooling for a polish, which resulted in downtime during manufacture.

A Fette 2090i high-speed compressing machine with industry standard B type tooling was used in the trial during the manufacture of a tablet measuring 10.5 mm round and weighing 3.46–3.66 g. I Holland provided a full set of punches including the new 
	XDF tooling.

The maximum press output of 150,000 tablet per hour (tph) was regularly reduced to prevent sticking as the formulation was found to have low hardness and friability issues. XDF tooling stopped the problem of sticking, while increasing output from 150,000 to 225,000 tph. The use of XDF improved compaction force dwell time by 44% and an output of 225,000 tph was achieved, an improvement of 50%. 

	Overall it has been demonstrated through rigorous trials that the use of XDF tooling helps to prevent sticking, friability, capping, and tablet hardness. XDF also enhances tablet compaction and cohesion and can increase dwell time on a standard punch type. This increase helps to solve compression problems without upsizing punches or investing in expensive modifications or new presses.

Larry L. Augsburger, Stephen W. Hoag, Eds. (CRC Press, Boca Raton, 3rd ed., 2008). 


	Vol. 42, No. 8
	August 2018
	Pages: 26, 28, 47

	When referring to this article, please cite it as R. Blanchard, “The Case for Extended Dwell Flat Tooling," 

Articles

Increasing dwell time can improve tablet production.

The Case for Extended Dwell Flat Tooling

The Tableting Science Anti-Stick Research (TSAR) program conducted by tablet-compression tooling manufacturer I Holland in collaboration with the University of Nottingham in the UK aims to investigate the common tablet-manufacturing problem of “sticking” (i.e., build-up of granule on the punch-tip) that can cause tablet-press downtime and reduced output. 
  
The causes of sticking are complex. Some of the underlying factors include the following:

 Elements within the formulation are naturally attracted to elements within the tablet punch material through Van der Waals forces. These low forces are measured in nanonewtons (nN), but in bulk behavior, these forces can cause sticking.

 Capillary action, which can be linked to high moisture content, creates the potential for sticking in both direct compression or wet granulation. However, if the granules are very dry, static electricity can form and cause sticking. 

The surface roughness of the contact affects sticking.

Under compression, the granule is either elastic or plastic, and these characteristics influence sticking. 

The TSAR project is developing a predictive tool that will use input parameters (e.g., surface chemistry, temperature, humidity, granule size, and whether the granule is elastic or plastic) to predict the sticking propensity of a given formulation. The tool can be used to optimize a punch or die-coating solution for sticky formulations.
  Several advanced analytical techniques have been used to understand the underlying causes of sticking. These techniques include optical surface profilometry, scanning electron microscopy (SEM), x-ray photo electron spectroscopy (XPS), atomic force microscopy (AFM), and time-of-flight secondary-ion mass spectrometry (TOF-SIMS).
  
  


  AFM works by scanning a probe with a sharp tip over the sample surface to build up a map of height and topography. The AFM uses an optical lever to monitor the motion of the tip mounted at the end of a reflective cantilever using a laser that is focused on the back of the cantilever. When scanning the surface sample, the tip undergoes upward and downward movements with the changes in the surface topography leading to changes in the deflection of an optical laser. The tip can be maintained at a constant force that allows real-time determination of height information or at a constant height to determine the deflection force above the sample. The images generated from the detector are three-dimensional topographical maps of the surface that are constructed by plotting the local sample height versus horizontal probe tip position (see 

TSAR researchers prepared adhesion maps for each coating at different humidities to measure the different adhesive forces on a tablet-punch face. The variance of these forces must be understood to be able to account for the difference caused by surface topography differences. 

In addition to these topographic measurements, the AFM can provide much more information. Because the AFM relies on the forces between the tip and the sample, it can be used to measure the long-range attractive or repulsive forces between the probe tip and the sample surface at a single point or across a surface, thus elucidating local chemical and mechanical properties, such as adhesion and elasticity, and even molecular bond rupture strength. The force is not measured directly, but calculated by measuring the deflection of the lever and knowing the stiffness (spring-constant) of the cantilever following Hook’s law: 

where F is the force, k is the spring constant (the stiffness of the lever), and z is the deflection distance of the cantilever. 

A force-versus-distance curve, such as shown in 

 typically shows the deflection of the free end of the AFM cantilever as the fixed end of the cantilever is brought vertically towards and then away from the sample surface. Experimentally, this is done by applying a triangle-wave voltage pattern to the electrodes for the z-axis scanner. This causes the scanner to expand and then contract in the vertical direction, generating relative motion between the cantilever and sample. The deflection of the free end of the cantilever is measured and plotted at many points as the z-axis scanner extends the cantilever towards the surface and then retracts it again. 
    
    

. The force-measuring principle of colloid-probe AFM is identical to that of a standard AFM, except particles are attached to AFM cantilevers and challenged to different surfaces. The drug-product particle is mounted onto the cantilever using a very small amount of glue. Once attached to the cantilever, the particle is brought into contact with the substrate (surface) and then retracted to determine the force of adhesion. This technique allows the quantification of the drug product adhesion to different surfaces in different environments.
    


    Time-of-flight secondary-ion mass spectrometry 


  TOF-SIMS is a sensitive surface analysis technique that provides information about material composition, molecular structure, and chemical bonding. TOF-SIMS allows a mass spectrum of a material’s surface to be obtained to a depth of approximately 1 to 2 nm. TOF-SIMS can also be used to “image” surfaces, thereby showing the distribution of selected ions on a sample surface. It is possible to image areas ranging in size from a few micrometers to tens of millimeters by rastering the primary ion beam over the selected surface. Due to the simultaneous collection of all the mass fragments, the resulting images have a full mass spectrum at each pixel allowing the retrospective visualization of any ion in the spectrum and its position on a surface. 

  
TOF-SIMS has the ability to obtain a depth profile and characterize a three-dimensional distribution of material components. A focused ion beam is rastered over a defined rectangular area on the surface of the sample to be analyzed (see 

). While the sputter ion beam is sputtering a crater, the analysis ion beam is progressively analyzing the center of the crater bottom. The intensities of the characteristic ions of each layer can be reported as a function of the depth, resulting in a three-dimensional cube representing the sputtered/analyzed materials. The mass of every secondary ion reaching the detector is collected and stored along with the x, y, and z spatial coordinates, thus forming a three-dimensional stack of mass spectra suitable for retrospective visualization of selected ions. TOF-SIMS allows the visualization of the chemical distribution of selected ions in three-dimensional volumes of the analyzed materials.
  
  


  Raman spectroscopy can be used for chemical identification, characterization of molecular structures, and identifying the effects of bonding, environment, and stress on a sample. XPS provides quantitative compositional information (e.g., amounts of elements and bonding environments) from the top 10 atomic layers of a sample surface. SEM employs a beam of highly energetic electrons to examine objects on a sub-micron scale and yields information about surface topography, morphology, composition, and crystallograpy. Laser profilometry is used to determine a surface’s profile to quantify its roughness.
  
  The TSAR project uses these techniques to look at particles that are stuck to a punch tip and analyze exactly what they are chemically, thus working out what those interactions are. 
  
 

PCA, a multivariate statistical technique, aims to generate correlations between XPS, Raman spectroscopy, and TOF-SIMS data to show quantitative chemical information for individual systems that might be involved in the adhesion problem of the powder with different coatings. PCA can be viewed as a method for reducing a large data matrix (i.e., a series of samples with varying secondary ion peaks) to a few key combinations of variables that describe the most significant trends in the data and identify a correlation between the different data obtained. It is a way of identifying patterns in data and expressing the data in such a way as to highlight their similarities and differences. Because patterns in data can be hard to find in data of high dimension, PCA is a powerful tool for analyzing data. PCA is used to understand the key interactions that are causing a formulation to stick to the punch tip faces and to develop the TSAR predictive tool.

Analytical tests, correlated with statistical techniques, are used to predict material behavior.