Oct. 14, 2020
MEDELPHARM's first live webinar is now available on replay.
On Tue. October 6th, Bruno Leclercq and Quentin Boulay presented STYL'One compaction simulation technologies and range of products to users and non-users of STYL'One .
MEDELPHARM Science Lab also shared 5 case studies (Particle morphology influence on tablet characteristics; Dry granulation feasibility assessment; Lubricant Efficiency; Rotary Press Comparison and Rotary press simulation) illustrating the use of the STYL'One series to take on scientists' day-to-day challenges.
The full video of the webinar is still available here, or you can take a quick glance at the transcript below.
[Stefan, host] – Introducing the Webinar
Good morning, or good afternoon everyone, depending on where you're joining us from and welcome to this webinar. My name is Stephen for business review and I will be your host. It is our pleasure to have MEDELPHARM with us today who will be presenting this webinar titled STYL'One a new approach to tablet formulation. Today's guest speakers are Bruno Leclercq and Quentin Boulay. Before we begin, I'd like to welcome you to our webinar platform.
You'll notice this webinar is browser-based, so if you disconnect for any reason, please just click on the link that you received by email to rejoin the station. In order to ask questions, you can send them in via the questions widget. Just type them into the box and click submit. You have until the end of the session to address any questions or thoughts that you may have. Please use the yellow help widget if you require any assistance and you can move resize and maximize any of the windows in front of you to get a better view of the slides.
But now please allow me to welcome Quentin Boulay
[Quentin Boulay, MEDELPHARM] – Presenting MEDELPHARM and STYL’One technology
Thank you, Stefan. Good morning and afternoon, everybody,
Welcome to the first webinar on “STYL’One, a new approach to tablet formulation”.
Today in this webinar, I will start with a brief introduction of MEDELPHARM, followed by the presentation of the STYL’One tableting technology to provide enough background before Bruno goes through some insight from our own science lab to highlight some experiments that you can perform on STYL’One. Finally, I will present you in two minutes the STYL’One product range before concluding and leaving about 15 minutes for a Q&A session.
MEDEPHARM is a technological company based on a mechanical engineering background. We are specialized in the design and manufacture of tableting solutions for R&D, scale-up and production support. It has been 20 years since the launch our first breakthrough solution with the STYLCAM, the first fully mechanical compaction simulator.
And since then, we’ve continued offering innovative and disruptive solutions to the market with the STYL’One series. This family of compaction simulators has been well accepted by the market, with more than one hundred and fifty units worldwide, and it became even more popular than the name MEDELPHARM itself.
So, you can see on the slide on the bottom left corner, the STYLCAM, then in the middle, the STYL’One classic on the top STYL’One Evo and the bottom right corner, the new product that we launched one year ago, the STYL’One Nano.
We've just moved to a new building in order to support growth and to host MEDELPHARM activities, including our innovation center with the design and development of STYL’One solutions and the associated software.
We have a team of engineers and web developers to develop the software. We have also our production workshop where manufacture STYL’One and offer aftersales services. We have our own science lab where we perform customer studies, machine demos and internal testing to support the design and development.
And the last business unit, with the distribution team that offers complete and innovative solutions in France and Belgium for powder processing from R&D to manufacturing. And it includes equipment for milling wet and dry granulation coding and more from the different brands that you can see on the screen.
We are selling directly the STYL’One in France and Belgium, and we have a global partners to support us all over the world.
It is the solution at a crossroads between R&D and manufacturing. On one side you have eccentric tablet presses. The most known would be the KORSCH XP1, which are useful to make tablets. But their limitations include working with only one compression profiles, at a limited compression speed.
You also have small rotary tablet presses with limited compression speed and instrumentation, but a higher production output.
On the other side you have the industrial rotary tablet presses, which offer a very high compression speed and production output.
So it is pretty clear and easy to understand that scientists will face issues, if they conduct their formulation development of an eccentric or small rotary tablet press as the formulation behavior will be impacted by the gap in compression speed.
In fact, moving from the large scale development to the full production scale is always challenging, and it requires solutions to reduce the risk during scale up. And here comes the STYL’One technology where you can R&D work and all your experiments, using manufacturing conditions.
STYL’One are compaction simulators, they are
single-punch R&D tablet presses.
So you can see on the picture that there is one station for compression with the upper and lower punches and the die in the table. We have fully instrumented tablet presses with force and displacement sensors in order to know the exact position of the punches and also the accurate force applied on the punches. When we couple this instrumentation with the powerful engine and drive system, it allows us to control the displacement of the punches in order to replicate R&D or production compression profiles at a high-speed. For example, in this video you can see that we simulate a Korsch XL400 at slow speed at 10 rpm and at 100 rpm.
So I will play it again so you can take a closer look at the slow speed here. And then at the higher compression speed, you can see the lower punch much faster.
Its versatility to fit current needs and upcoming needs. You only need one piece of equipment if you want to characterize your API, evaluate your formulation, determine your process parameter, or support your production floor by resolving capping issues, for example.
You only need one piece of equipment if you want to perform single layer tablets or move to more complex forms like multilayer or press-coated tablets that are also known as tab-in-tab.
You only need one piece of equipment if you want to assess the feasibility of a dry granulation process or look at external lubrication. But we, at MEDELPHARM, we don’t plan on stopping here. We want to continuously offer new solutions to fit evolving needs with the same STYL’One philosophy, which is also something unique!
All our developments are made with the ease of use and the intuitiveness in mind, to offer technology for all. It doesn't matter if you are a beginner in the tableting world or if you have 20 years of experience, you can access the tableting technology.
We also keep flexibility and compatibility in mind to offer all-in-one solution with accessories and software modules to fit your needs. There's no need to buy a new machine if your needs evolve. You only need to change the configuration of the existing STYL’One by changing accessories or adding new modules.
Low maintenance is key compared to non-mechanical compaction simulators with only a few points of preventive maintenance. And besides reducing risks during scale up, with a better knowledge of your formulation, scientists can perform more experiments in a day. So in short, STYL’One is a time and cost-saver.
To give you an example of customization and flexibility, and because operator safety is a must now, especially with the increasing demand in High Potent API, STYL’One has been designed to work in different safety configurations. We can work with a small amount of power in a small compression area to limit the exposure. We can flood the compression area with nitrogen if we use explosive powders or oxygen-sensitive products.
But we can also go to a full OEB 5 solution with an isolator around the STYL’One, as you can see on the picture on the right of the slide.
I will now hand over to Stefan for a quick poll question. So Stefan, take over.
[Stefan, host]- Presenting poll question
Thank you very much, Quentin.
So the poll question is: “Are you using a compaction simulator, yes or no? “ Quentin, why did you chose to ask that question in particular?
[Quentin Boulay, MEDELPHARM]
We would like to know our audience a bit better to know the way you work and if you are using your compaction simulator in your daily experiments to adapt a bit the presentation that we will make with the case studies in a minute.
Thank you very much. And now let's take a quick look at the results, so 42 percent of the audience said yes and 57 percent said no.
Now, over to you, Bruno.
[Bruno Leclercq, Medelpharm] – Presenting 5 case studies
Ok, thank you. We were expecting percentage to be either on the low side or the high side. But now, we have a 50-50. For the rest of the presentation I will show you some of the case studies that we done in our lab. And I hope you will all enjoy the rest of the presentation.
I will share with you some studies that we're performing in our Science Lab, using the STYL’One technology.
In the first example we look at various grades of Mannitol and more specifically, the importance of particle morphology on tableting behavior.
The second example we will show you how feasible assessment of dry granulation can be done at the development stage and especially using a small amount of material.
The third example will show you the importance of lubricant. Indeed, lubricant is well known to be an important excipient in a formulation and the choice of the typeor quantity of lubricant can be really critical.
In the fourth example, we will look at a comparison of 2 tablet presses.
Rotary tablet presses in production could be seen as a spinner. However it is important to assess if the tablet produces a similar tablet properties if it's produced with one tablet press or with another one.
And the last example will show you how to evaluate, mitigate risks during scale up.
Those are just a few examples of what we do in our Lab. But if you have any other requests, feel free to contact us.
In this first example, we investigated the effect of Mannitol production processes and particle distribution on tablet properties.
Mannitol is a well-known excipient. It is a polyol, typically used in formulation like chewable formulation, but can also be used to replace lactose.
Two processes can be used to produce some Mannitol.
The first one is spray-drying. Spray-dryed materials have been developed to increase and control the particle size and to also improve the compactibility while maintaining a good flowability.
The second process to produce mannitol is by crystallization. Crystalline grade are typically milled or sieved to obtained different ranges of particle size
In this study, we compared two grades of spray dry material and three grades of crystallized mannitol.
The graph of the hardness versus compression force applied (or so-called manufacturability) is showing a clear difference between the two production processes. The crystalline grades, which is no surprise, is giving a low compactibility versus spray dried material.
But if we focus on the crystalline grades, it can be observed that the particle size has an influence on manufacturability. Decreasing the particle size shows an increase in the tablet hardness.
Besides comparing excipients, a similar study can be done to compare impact, for example, of a change in the production process. For example, if you're changing the type of mills you use, if you are changing the milling conditions, it is always interesting to look to the tablet properties to see if a change in the production process had an effect on your final formulation.
Now, let's move to the second example.
The second example would be determination whether a drug or an excipient mix is suitable for dry granulation.
And this will also be an example to show you what you can do that with a limited amount of product.
Feasibility assessment of dry granulation is often done by using a roller compactor. There are different types of roller compactors available on the market and they differ by their design.
Dry granulation is used in order to modify powder properties in order to increase bulk density, improve flow, or reduce segregation.
Principle: The powder is fed between the two counter rotating rollers and a compact is produced under pressure. However, this kind of process requires a large amount of powder not always available at the development stage for reason of low availability or sometimes costs of an API.
By using a compaction simulator we can mimic the compaction profile of a roller compactor while using a small amount of powder.
When we say we can mimic a roller compactor that means that we can achieve the same symmetrical compression, and we can achieve the same densification factor, that will be obtained on a roller compactor.
In production, Dry granulation is done by using a roller compactor to produce ribbons .The ribbons produced are then milled often by the mill located below the rolls of the compactor to produce granules.The granules are then blended with external phase or lubricant before compaction on a rotary production press. In this case, to do a granulation process you need one roller compactor and a high speed tablet press
With the STYL’One we are going to mimick both the compactor and the tablet press with one equipment.
First we make ribbon at specific solid fraction on the STYL’One. And then, offline, we will mill the ribbon to make some granules. The granules are then blended with external phase or lubricant before compaction on the Styl’One to mimic rotary tablet press you will be using or you want to use in production
The last step is characterization of your tablet produced. The Results will tell you if roller compaction is a feasible process for your formulation. If not, you can either modify your formulation by changing the excipient or the ratio between the two different excipients or go for another process, like wet granulation.
With the STYL’One we are going to mimick both the compactor and the tablet press with one equipment.Bruno Leclercq, MEDELPHARM Science Lab
Let's now look at a real example:
On the left hand side, you see a screenshot of the software that will guide us to produce ribbons at different Solid Fractions.
The software gives us different fraction, but the one we have used in this study, is the one where we target a certain gap, like on a roller compaction, and a certain solid fraction (or relative density). And the software will find the pressure needed to achieve the desired solid fraction.
In this example, we are mimicking a specific roller compactor at a gap of 2 mm and we are targeting a solid fraction of around 0.7. We also produced ribbons at 2 other solid fractions, respectfully at around 0.8 and 0.9 by increasing the pressure applied.
Solid fraction is one of the most important Process Parameter in roller compaction operations. That's why it's important, when we do this study, to try to work by targeting solid fraction.
The question that the formulator needs to answer is what range of solid fraction is acceptable for my formulation taking into account compactibility but also other parameters like friability or dissolution.
During scale up, the ultimate the goal will be to target same solid fraction as the one optimized during the development in order to achieve similar granules and similar tablets properties.
If you now look at the results of
this study. We have produced ribbons at different solid fractions. Then we took
these ribbons at different solid fractions then we milled them in a Quadro
Comil to obtain granules. And then the granules were then compacted on the
Let’s now review the results.
We can observe that tablets produced with the granules compacted at a solid fraction of 0.85 presented the lowest tablet breaking force. And this, again, is not surprising, has been published many time in the literature.
Why? Because high pressure applied in to production of ribbon often lead to a reduction in re-compactibility, especially if the formulation shows plastic deformation.
In this case, solid fraction seems to be the critical process parameter. We could therefore decide to target a solid fraction between 0.7 and 0.8 in production to avoid loss of compatibility during tableting. But other properties have to be taken into account as disintegration time and dissolution rate are also critical.
The conclusion that this study is that dry granulation is feasible process. And we could with this work already determine some of the setting and critical process parameters for technical transfer.
Let's move now to the third “example” or “case study”.
This case study will be talking about lubricant efficiency. In this case, we look at the influence of the lubricant type on ejection force, hardness and disintegration time.
Tablet lubrication is performed to reduce friction between tablet and the die during ejection phase. Tablet lubrication is commonly achieved by incorporating a lubricant to a final blend prior to tableting.
In this study we compare lubricant properties on a standard blend. The lubricant level was kept a level of 0.5 %, and we can observe different things.
First of all, the ejection forces are decreasing when compression force are increasing. This is link to a reduction of the tablet thickness leading to a reduction of the contact surface between the compact and the die. But the clear conclusion of this graph is showing that lubricant 3 is clearly showing a higher lubricant efficiency.
However at this stage we cannot for sure decide which is the optimal lubricant as we need to look at other parameters. And obviously, when you look at other parameters, the first one that we need to look at would be the hardness and we also would have to look at disintegration time.
Because lubricant can impact the quality of the tablets: decrease the hardness, increase disintegration time, or reduce dissolution rates.
In this study a reduction of the tablet hardness can be observed depending of the lubricant used. As you can see on the plot, the lubricant 3 has a high manufacturability and the lubricant 2 has the lowest one.
However, at this stage, especially because the tablet hardness are quite high in this study, it is difficult to actually decide on or to eliminate one lubricant. However, when we look at the disintegration times, we can see a significant difference between the different lubricants.
The lubricant 2 shows less impact on disintegration time and maybe that could be linked to the hydrophilicity or the hydrophobicity of the lubricant. The other two lubricants (lubricant 3 and lubricant 1) are clearly showing a major impact on disintegration time and especially the lubricant 1.
In conclusion even though the Lubricant 3 shows high lubricant efficiency, it also influences the disintegration time and therefore might not the ideal lubricant to be used in your formulation.
Evaluation of a lubricant can easily be done by looking at ejection forcesBruno Leclercq, MEDELPHARM Science Lab
If we now look at the influence of lubricant concentration on ejection force and hardness.
In this case, we see clearly that a low level of lubricant at 0.5% is showing a certain ejection force. If you increase the level of lubricant to 1.5% or even to 2.5%, you see a drastic reduction of the ejection force. However, it has to be noted, there's no need to go above 1.5% because if you look at the 2.5 of lubricant, there's no reduction in the forces. However, if we look at the manufacturability, you also see the same trend as we've seen before. In this case, if you look at the lubricant level of 0.5 versus 2.5, you see that if you increase the level of lubricant, you can see a reduction in the hearts of your tablet produce.
Therefore, evaluation of lubricant can easily be done by looking at ejection forces and also if required, we can look at other things, we can look at the ejection signals. Because not only the maximum ejection force is important but the shape of the ejection signal might be critical. All those data can be easily extracted and analyzed by the formulator during his development process.
Now, let's move on to another topic. We will now study a comparison of 2 different rotary tablet presses.
In this example, we will compare 2 tablet presses: Tablet press number 1 and tablet press number 2.
To introduce the study that we have done, let me show you how we did it.
The STYL’One can mimic compression cycle of rotary tablet press. And that’s done by simply selecting the profile of the tablet press you want to mimic in the software.
The graph that you see, shows the displacement of both the upper and lower punches and all the different part of the compression cycle of the tablet press you selected. You see: the precompression; the relaxation between the pre- and main compression; the compression itself; the relaxation between the compression and the ejection; and the ejection itself.
The methodology used was to perform a compaction study for each rotary press with the same compression time and check the hardness of the tablets as well as the ejection forces.Bruno Leclercq, MEDELPHARM Science Lab
By using the profiles of two presses, we can produce tablets using compression cycles mimicking the two rotary tablets presses we want to compare. Then tablets will be characterized to see if those 2 presses give similar results.
The objective of this study was to evaluate the difference of two well known production presses to assess how the dimension of the pre-compaction and compaction rolls, their positions and the slope of the ejection ramp can impact the properties of the tablets.
The methodology used was to perform a compaction study for each rotary press with the same compression time and check the hardness of the tablets as well as the ejection forces.
In the first graph (the manufacturing graph), you can clearly see that there’s a difference between the 2 tablets we’ve been making with the tablet press number one versus tablet press number two. However, if you look at another parameter, in this case the ejection force, there is no significate difference between the 2 tablet presses.
And if we now move to another graph, and this graph is really the one where we’re going to compare the different cycles between press number 1 and press number 2. And the reason to look at this, is to try to understand why we did see a difference in terms of hardness between the 2 rotary tablet presses.
If we compare the profile of the 2 tablet presses, we get the same pre-compression time; similar compression time ; same relaxation time between the compression and the ejection; and similar ejection ramp. The only parameter that we notify to be different was the difference in the relaxation time between the pre compression and the main compression. And in this… well we did no go through it, but the graph is leading us to the hypothesis that the difference in the relaxation time between the pre compression and the main compression could explain the difference in the final hardness observed.
If further study, for example, extending the relaxation time between the pre and the main compression is needed just to try to understand to see how far should we go to maybe see a difference between different tablet presses. That could be done by modifying to compression profile itself, but keeping all the other parameters constant.
As a conclusion, a compaction simulator is a perfect tool to find the best parameters for your product. And, as a consequence, to speed your scale up work.
Case study #5: Rotary press simulation
Let's move on to the last case study. I will be showing you work that's been shared with us by Skyepharma, a CDMO based out of France.
They have performed a comparison of the Dissolution Profiles between tablets made on STYL’One tableting instrument and tablets made on an industrial rotary tablet press.
Mimicking a production process can be achieved simply by selecting the compression profile of the industrial tablet press you want to mimic.
The first case study was to mimic tri layer tablet press and the second one was to mimic a tab-in-tab tablet press. The graph on the left. It was a Tri layer tablet with biphasic release. And it has been made has been made on a STYL’One Evolution and on an industrial tablet press.
The APIs are located in the layer 1 and 3 while the center layer, was a neutral layer to avoid any interaction between the two APIs
The conclusion by Skyepharma on
this study was that the dissolution rate of the API’s are similar between the
tablet made on the small scale and on the production scale. This was for them a
good way to be sure that the work done in development can translate to
On the second graph on the right, the formulation is an inner core entrapped into an outer shell. This is typically called Tab-in-tab or press coated tablet.
In this case again, the dissolution rates of the API are similar between what was done on a STYLOne Evolution and on a production press
The outer shell, in both cases, started to disintegrate at exactly the same time.
As a conclusion, and that’s the conclusion of Skyepharma, STYL’One Evolution compaction simulator can mimic the behavior of tablet right from the R&D phase. This is one example of a reduction in cost and time and material during the development process. Those are important parameters for the formulator.
Now, I will hand over to Quentin for the rest of the presentation.
[Quentin Boulay, MEDELPHARM] – Concluding & presenting the differences between STYL’One Evo and STYL’One Nano
Thank you Bruno for presenting us these five case studies that are only examples of that we can perform on the STYL’One compaction simulator.
So here is just a quick summary of what differentiates STYL’One Evo and STYL’One Nano, the two products that we have in the STYL’One family. So on the one hand, you have the STYL’One Evo which is the most versatile compaction simulator with multi-layer capabilities. On the other hand, the STYL’One Nano is the most advanced benchtop research press, with unique compression dynamics and simulation capabilities.
STYL’One Evo, as a multi-functional tool, can be utilized from early research to scale-up and production with GMP module, for example.
While STYL’One Nano application will be focused on early research and formulation development due to a difference in simulation capabilities.
STYL’One Evo compression speed is higher than the compression speed of the Nano; and we have slight differences in terms of compression profiles. The STYL’One Evo can accommodate production press and roll compactors on top of R&D compression profiles (like V-shape or extended dwell-time or square profiles that are used in early research and development)
STYL’One Nano is a single layer tablet press while STYL’One Evo can perform more complex tablet forms like multilayer (up to 5 layers) or press coated tablets (tab-in-tab).
And finally, something that also differenciate the two products is that STYL’One Nano, as a benchtop unit, can be easily placed into a downflow booth for reduced operator exposure. And the STYL’One Evo has several containment options, as we explained earlier, from simple negative pressure to a full OEB-5 solution.
As a conclusion, MEDELPHARM, has been committed for the past two decades to developed STYL’One tableting solutions for R&D, scale-up and production support. To accelerate formulation development for oral solid dosage forms. To reduce risk of failure during scale-up with a better understanding of your formulation. To decrease development time with less surprise when you move to scale up. To solve production challenges such as capping or lamination.
STYL’One Evo can perform complex tablet forms like multilayer or press coated tablets (tab-in-tab).Quentin Boulay, MEDELPHARM
The STYL’One technology has been designed as an all-in-one solution and it's ready to accommodate future developments. We will continue to develop solutions to meet growing and evolving needs, especially for example in containment solutions, as it is a clear trend now. And to conclude STYL’One Tableting Technology is the worldwide reference to drive decision making for scientists from early development to manufacturing. We have more than a hundred and fifty units all over the world, and different type of customers in the pharmaceutical industry, but also in a in other industrial applications.
I'd like to thank you for your attention. If you want more information about our science lab studies or STYL’One compaction simulators don't hesitate to contact us. You can see our contact details in the slide now.
Now it would be time for Q&A session. So I will hand over the presentation to Stephen, who will ask the questions