A Little Thought Goes a Long Way in Tableting

Published on: 
Pharmaceutical Technology, Pharmaceutical Technology-04-01-2020, Volume 2020 Supplement, Issue 2
Pages: s14–s16

Understanding formulation properties early in development can prevent some costly issues later on.

Oral solid dosage forms remain the most popular within the pharmaceutical industry as a result of convenience of administration and general acceptance with patient populations. With speed-to-market becoming an ever more pressing matter for drug developers, a more complete understanding of material properties as early in the development cycle as possible can avoid potentially costly tableting pitfalls.

“Tableting has been around for more than 100 years, and at its core it seems quite easy, but if you don’t really understand the material properties, there is a chance that you could reach commercialization and end up with a formulation that is not suitable for tableting,” explained Elaine Stone, Merlin Powder Characterisation, during an event sponsored by Catalent in Nottingham, UK in December 2019 (1). “A little bit of thought about what properties a formulation needs to have at the beginning can really help the tableting process.”

Tablet basics

“For those that don’t know so much about tablets, they are quite complex little things, so when they are popped out of the wrappers from the pharmacy they appear simple, but there are a lot of different ingredients that have gone into them,” Stone said. “Some of these ingredients are really good for tableting, and some are really bad for tableting but good for other things. So, we’ve got a combination of all sorts of different ingredients in there, and to get a really good formulation for tablets we need a suitable balance of these ingredients.”

In terms of tablet strength, Stone explained that it is necessary to have a formulation that will be strong enough to form the tablets and be transportable without breaking, yet also break up fast enough so that the drug is bioavailable once swallowed. “There are these two competing properties within a tablet formulation that we need to balance, which can be achieved through understanding both mechanisms,” she added.

Some of the issues that can arise from poor tablet compression understanding include a formulation that cannot run on a tableting machine, tablet sticking, tablet capping, and reduced press speed, which are all costly, Stone emphasized.

Compression factors

“There are two main factors involved in tablet compression,” Stone continued. “The first is deformation and the second part of it is persuading all of those particles to bond back again with each other to form a solid compact.”

Particle deformation. There are three main ways for a particle to undergo deformation-elastic deformation, plastic deformation, or brittle fracture. “The first one, elastic deformation, means that when the formulation is compressed, it changes shape, but as soon as you release the compression force the substance reverts back,” Stone confirmed. “This type of deformation is a challenge to deal with from a pharmaceutical point of view because we want permanent change. Therefore, elastic particles, such as starches, can be problematic for tableting.”

If a particle exhibits plastic deformation, there will be a permanent change of the particle’s shape; Stone noted that these particles tend to be quite soft and pliable and can deform at low compaction forces. “For brittle fracture, stresses during compression include crack propagation along the particle or granule, and the end result is fragmentation,” she said.

However, many materials do not precisely match these categories, which means a way of investigating how a particle may behave when compressed is required. “We can investigate a little bit more by performing the Heckel test,” Stone added. 

The Heckel analysis was originally created for metallurgy but was adopted by the pharma industry to assess compression properties of materials (2). The analysis basically involves compressing material and then plotting the relative density of the material against punch pressure (2). “We take a small amount of material-it takes less than three grams to do a Heckel test-we compress it at a constant speed, and then we calculate the yield pressure,” Stone said.


“Lots of materials can be sensitive to speed of compression,” Stone added. “If you have assessed the material in a lab setting on a small piece of equipment, it is possible that the material will behave differently once you scale-up onto a larger piece of equipment that has a faster running speed.” 


A way to combat this potential discrepancy is to perform the same test at production relevant compression speed and compare the changes in yield pressure to determine the strain rate sensitivity (3). Once plotted, in a graph of strain rate sensitivity versus yield pressure, it is possible to categorize materials and determine whether you need to balance out the formulation to improve tabletability. 

“If you have identified a material and it has properties that are not necessarily ideal for tableting, you can decide to add in different ingredients to balance it out,” Stone said. “So, if you have a material that is too soft and plastic you might want to add in some brittle materials, or vice-versa, to balance the formulation and make it more suitable for tableting, for example. Therefore, through identifying the material characteristics you have a good idea of where to start with the formulation design.”

In addition to compression speed, yield pressure can be impacted by a few other things, such as materials that are polymorphs or salt forms, the moisture content of the material, particle size, or particle shape. “Moisture is a plasticizer, so it can lower the yield pressures, and particle size can be quite important, particularly if micronization is involved, because really small particles behave completely differently sometimes to the larger particles from which they originated,” Stone confirmed.

Bonding and tablet strength. During compaction, when the particles have deformed and fragmented and moved closer to each other, with the compression forces being applied, bonds are formed between the particles. As the number of inter-particulate bonds increase, then so too does the strength of the tablet.

“What we are trying to do during tableting is reduce the volume of the formulation blend and promote bonding between the different ingredients,” Stone said. “The success of tableting-deformation and bonding-can be measured by looking at the tensile strength.” 

In essence, when plotting the tensile strength as a function of compaction pressure, it becomes apparent that on increasing the compression forces, the compact thickness decreases and there is a region where the material has tablet-

like properties, which is desirable for tableting. If there is insufficient force applied, the tablets will not be formed, and if there is over-compression, then capping and lamination can occur. “If the process is in the over-compression region, then it is on the edge of failure all the time,” stressed Stone. “This can lead to tablets that look ok but perhaps have cracks and deformities within that cause capping and lamination.”

Formulation design

It is possible to use various data from compaction simulators to help determine whether the formulation design will be viable for a tableting process. Tabletability is an assessment of the tensile strength versus punch pressure; compactability is solid fraction versus tensile strength; and compressibility is punch pressure versus solid fraction.

When assessing tabletability, small batches of formulation are needed and it is possible to make the tablets at different speeds and see whether or not an appropriate tensile strength is achievable. “Although it is recommended for a formulation to be able to achieve a tensile strength of at least 1.7 MPa, it doesn’t necessarily mean that the production target needs to be the same,” Stone said. “However, if the formulation cannot achieve good strength then there will probably be issues during production.”

Compactability, which is independent of the speed of manufacture, can be used to explain the impact of density on tablet hardness. “It is possible to perform a roller compaction simulation to show how the blend will perform,” added Stone. “This performance can then be compared against all the different solid fractions, and all the various options that are available for the formulation blend will be apparent.” As an example, a potential roller compaction blend with a low tensile strength would be indicative of a blend that will not provide robust roller compaction ribbons-the ribbons will mill to very fine powders-so it may be worthwhile to use different binders or fillers in the formulation to improve the tensile strength.

“Compressibility is really good for our understanding of press process and understanding of the settings that may be required when scaling up,” explained Stone. By looking at compressibility, material wastage can be avoided during process set-up as it is possible to work out what might be required to achieve the desired solid fraction.


Useful tool

“Compaction simulation can be used in early development and only requires small amounts of material,” said Stone. “It’s really useful to understand the drug properties that you have before you start formulating, but compaction simulation can also help you to predict what is going to happen with those formulations at early stages, when there is a chance to alter the blend.”

“Additionally, compaction simulation can be used to predict scale-up behavior and optimize the properties of new molecules in production,” she added. “Furthermore, compaction simulation is pretty fast and saves on materials.”


1. E.H. Stone, “Compaction Simulation in Early Development,” Presentation at Recent Advances in New Drug Development (Nottingham, UK, December 2019).
2. R.W. Heckel, Transactions of the Metallurgical Society of AIME, 221 (5) 1001–1008 (1961).
3. R. Roberts and R. Roe, Chem. Eng. Sci., 42 (4) 903–911 (1987). 

Article Details

Pharmaceutical Technology
Supplement: Solid Dosage Drug Development and Manufacturing
April 2020
Pages: s14–s16


When referring to this article, please cite it as F. Thomas, “A Little Thought Goes a Long Way in Tableting,” Solid Dosage Drug Development and Manufacturing Supplement (April 2020).