Transcript - Impact of Geometrical Process parameters on the tab-in-tab structure

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Feature article


July 23, 2021

On June 9th Léo Picart, Phd Student at Skyepharma / University of Bordeaux, Aline Moulin from Skyepharma and Bruno Leclerc from MEDELPHARM animated the webinar on the impact of geometrical process parameters on the tab-in-tab structure.

You can access a transcript of the webinar below. 

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Transcript – Impact of geometrical process parameters on the tab-in-tab structure


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Full webinar available

Read below the webinar’s full transcript


[Nick Robertson – BUSINESS REVIEW] – Introducing the webinar   
Good morning or good afternoon everyone, depending on where you're joining us from today. Welcome to the webinar. My name is Nick from business Review and I'll be hosting. It's our absolute pleasure to have MEDELPHARM and SKYEPHARMA who will be presenting the webinar titled "Impact of geometrical process parameters on the tab-in-tab structure”. Today's guest speakers are Léo Picart, PhD student at SKYEPHARMA and the University of Bordeaux - 

Hi, everyone, hope you're doing well.


[Nick Robertson – BUSINESS REVIEW] 
The next speaker is Bruno Leclercq, Science Lab Head and Business Development Manager at MEDELPHARM. 

[Bruno Leclercq – MEDELPHARM]
Good afternoon


[Nick Robertson – BUSINESS REVIEW]
And the third speaker will be Aline Moulin, Pharmaceutical Development Director at Skyepharma.


[Aline Moulin   – SKYEPHARMA] 
Good afternoon everyone.

[Nick Robertson – BUSINESS REVIEW]
I'd like to welcome everyone to our webinar platform "On 24". You'll notice that it is entirely browser based. So if you disconnect for any reason, or come into any problems at all, either click on the link that you received in the email to rejoin the session or click Refresh. In order to ask any questions, you can send them in via the questions widget, which should be in the top right of your screen - all you have to do is type your question in and click enter or submit and it will come through to us. If you do need any help at all, please use the yellow help widget which should be on the bottom hand side of your screen. And also remember you can move, resize and maximize any of the windows in front of you by clicking on the corners and just dragging to get a better view of slides or a better view of the webcam. But for now, please allow me to welcome Aline.

[Aline Moulin   – SKYEPHARMA]
Okay, so thank you to everyone for joining me for this webinar, a joint webinar between Skyepharma, MEDELPHARM and Bordeaux University. The general topic is press-coated tablets or tab-in-tab which are of great interest in the pharmaceutical industry, especially for the design of controlled release formulations. And today, I will particularly focus on the impact of geometrical process parameters on the tab-in-tab structure. So this webinar will be divided into four parts: the first one will answer the question why develop a press-coated tablet, with an example of a commercialized product. Then we have the presentation of the STYL'One Evolution as a key technology to develop this type of formulation. Then Léo will present some very interesting resultsfrom his PhD studies . And we'll be very happy to answer your question. So, to start a short presentation of SKYEPHARMA.

Introducing SKYEPHARMA and their technologies

[Aline Moulin   – SKYEPHARMA]

So SKYEPHARMA is a pharma service provider with a specific expertise in complex oral solid dosage form, so we perform trials from development, early-stage, scale-up, transfer, commercial manufacturing and packaging and we also provide support services such as supply chain, quality and regulatory. So depending on the needs of our clients, we provide a fully integrated one stop shop services or tailor made solution. 

SKYEPHARMA is well known in the CDMO marketplace, all development teams with experts in formulation, Quality by Design, scale-up, in particular the development of controlled release oral dosage form. For this purpose we use development equipment such as described in this slide and in particular for the tableting process we are equipped with a STYL'One Evolution with multilayer and press-coating modules

So to maintain our expertise and scientific excellence, we have some collaborations with academic laboratories - for example with Bordeaux University with Prof. Tchoreloff's team. SKYEPHARMA is financing a PhD study on tab-in-tab compression process.

So an example of two technologies developed and patented by SKYEPHARMA.


So the first one is GEOCLOCK® - a press-coated tablet technology and a way to obtain delayed release formulation & delayed release dissolution profile - so single pulse or double pulse on the left of the slide.

On the right is an example of GEOMATRIX® multilayer tablet technology, which allows me to obtain sustained release dissolution profile. So this can be applied with one API or two APIs. One thing to note is that these technologies are already industrialized, that means that today on our site, we are able to manufacture at industrial scale this type of complex tablet, they are currently on the market. 

Tab-in-tab vs multilayer STYL'One

Press-coated and multilayer tablet made with STYL'One Evo compaction simulator

So an example of GEOCLOCK® - press-coated tablet currently on the market - is Rayos®. It is a press-coated tablet containing prednisone, it is used to treat inflammatory diseases and in particular Rheumatoid Arthritis. These types of diseases display symptoms that are more acute in the morning, such as pain and stiffness. And so Rayos® helps with this specific formulation to reduce the symptoms, which are typically more severe in the morning.


So how does it work? So, Rayos is the first and only delayed-release form of prednisone, that means that it works like traditional prednisone, but it is different because of its unique formulation, which is delayed release. We have the prednisone release about 4 hours after administration. So this is illustrated in this slide. 


So if you take the Rayos at 10pm, just before going to bed, you will have the prednisone release start at 2am and the major peak at 4 am. That is corresponding to the timing when the Rheumatoid Arthritis symptoms rise. So this type of release is more convenient than immediate release - morning or evening dosing - because for both immediate release, that will be too late or too early compared to the inflammation. 

So that is an example of a dry product that is already on the market. At SKYEPHARMA we have several other projects that are currently under development with this type of formulation. For this, we need rapid and flexible prototyping, that help our client to save pharmaceutical development, time and budget. And the key equipment for that is the STYL'OneEvolution that we have in our lab, which allows to reproduce industrial tableting processes. So now I will give the lead back to the moderator who has a short question for you.

[Nick Robertson – BUSINESS REVIEW]

Thanks Aline.

So guys, now we have a poll question for everyone. So you should be able to see it here. So everyone, you should be able to see the first poll question.

And it reads: "Have you ever considered press-coating (tab-in-tab) as an option for your controlled release tablet development"? So I'll just give everyone about 30 to 45 seconds to cast their votes. And then I will move to the results area. And we'll then discuss.


[Bruno Leclercq – MEDELPHARM]

The idea of asking the question is to understand if you've been aware of press-coating as a technology to produce tablets.


[Nick Robertson – BUSINESS REVIEW]

Sure, fantastic, guys. We'll now move over to the results section. I'll just pop the slide over now. And here we go.

[Bruno Leclercq – MEDELPHARM]

Okay, I see that we have like 40% of the people who know about press-coated tablets but we also have quite a lot of people who are not aware of press-coated tablets and in the next 30 minutes you will have the chance to learn more about this technology. And before Leo's presentation, let me first introduce the STYL'One Evo, a key technology to develop classic but also complex oral solid dosage forms.

STYL'One Evo: a key technology to develop complex oral solid dosage forms

[Bruno Leclercq – MEDELPHARM]
Before diving into the application of press-coating, let me first introduce the STYL'One Evo.


STYL'One Evo is the most versatile compaction simulator. And the picture you see on the left is a picture of the STYL'One Evolution.
Typically the STYL'One Evolution is connected to a laptop. But in this instance, this is a special execution, which is done for GMP area, where you see the difference being that we have a special keyboard and a special screen to meet the need of GMP requirements, especially in terms of cleaning.

STYL'One Evo with GMP requirements

STYL'One Evo with GMP requirements

Now let me go quickly to the key elements of the STYL'One Evolution. The STYL'One Evolution one is a single station tablet press, which has been designed to formulate a single layer, multilayer, but also tab-in-tab with the same equipment.

The beauty of it is that you even if you only have a small amount of material, you could do all your characterization of your formulation.

Also, due to the fact that the STYL'One can run at very high speed, we can actually mimic rotary tablet press. And therefore when you do your development, you can actually do your development at the speed of the production press. And this will enable you to really test the robustness of your formulation. It will obviously add to reducing your development time, but also helping you to get a reduced risk during scale-up.


Last but not least, if you're working with high potent API and because safety should be the first priority of all of us, we actually have developed a STYL'One which is a fully contained, that's the one you see on the picture and you actually see the STYL'One in the middle and outside you have the isolator. Now I'm going to play a short video to explain the tab-in-tab.

[Edit: access tab-in-tab video on our Youtube channel HERE]

Tab-in-tab is plug and play, can be used for R&D, clinical supply, troubleshooting, you can use flat & biconvex cores. The software will help you to develop your process parameters but also configure the different layers of your tab-in-tab: Filling of the first layer, adding of the core, tamping, adding the last layer, and your tablet is produced.


Now let's see the key user benefits for press-coating formulation development.

Key User benefits of STYL'One Evo to develop press-coating formulation

First of all, with the STYL'One you're able to actually do proof of concept or prototyping. And this is really important at the beginning of the process. After the proof of concept, optimization of the core could be done, and also optimization of the outer layer will be key to achieve your targets in terms of tablet properties and dissolution profile.

And if you need to produce a small technical batch, this could be done also with the STYL'One without the need of using a rotary tablet press from your production line. The tab-in-tab option is compatible with any of the STYL'One - if you already have a STYL'One and you want to do press-coated tablets you have to acquire the tablet loader & the software and you will be able to actually do some development of press-coated tablets.

When you are doing your development, you need to do a quick assessment of your process parameters and the influence on quality attributes. I'm just going to, to go through a couple of parameters which are important.


Obviously, you need to look at the layer thickness, you need to look at the force applied - the tamping force (pre-compression & main compression force) and the compression speed. One thing that is really important is the core position - thanks to the core loader that we have we can position the core at the center of the tablet, or whether during the development it's also very important that you also test if your core is off-center. And also especially looking at the impact on your target tamping, compression speed, but also on your dissolution.

tab-in-tab different core positioning

Choose core positioning easily thanks to STYL'One Evo's tab-in-tab accessory

Last but not least, when you've done your development, you know that you're ready to go to a production press. And thanks to the fact that with our software we can actually mimic production press that make press-coated tablets, you simply have to select the profile of the tableting machine that could do tab-in-tab in production, and you can actually run your formulation with this profile, to try to decrease the risk you may have when you scale-up and you go to production.


Like I said, I did show you a few process parameters that are important, but Léo will now in his presentation highlight some process parameters that have never been completely understood and studied. And now up to Léo for his presentation.

Impact of geometrical process parameters on the tab-in-tab structure

Fundamentals of press-coated tablets


Thank you for your introduction. I will now present the results of a research study that we lead in University of Bordeaux with use of the STYL'One Evolution and precisely the impact of geometrical process parameters on the tab-in-tab structure.


First of all, I'd like to do a quick introduction on press-coated tablets, what is it and what is the purpose of this tablet.


So, the principle is from a core tablet - a single tablet - to form a solid coat around it. To continue on what Aline said earlier, it is of high interest for modified release applications because you go from an immediate release in the case of single tablet to a pulsated release in the case of press-coated tablets. You know there is a whole time called lag time where the shell remains around the core, and allows no active to go in the liquid. So as Aline said, again, it is used to treat diseases with night or morning symptoms like rheumatoid arthritis, apnea, Prinzmetal's angina or asthma.

I will now detail the steps of the production of a press-coated tablet. So the first step is of course to compact the core. It is done on a separate machine as the press coating because of course the core has to be smaller than the whole press-coated tablet. In the case of STYL'One Evo, you just have to change the tooling, and in the industrial production, it's on separate machines. Once you have the core, you deposit it on the first powder bed, then it is litely tamped into the powder bed and then you can process to the second filling of powder above the core. And finally, the punches are doing the main compression which is called coating compression. 

So what are the objectives of our study?

It is that some parameters have not been yet studied on the design of tab-in-tab and especially geometrical parameters, like the thickness of the layer, like how thick is the powder above the core and the ratio between the core diameter and the shell diameter. So, this will be a fundamental study with model excipients to precise the rule of these parameters on the structure and properties of the core and shell after compaction and more generally to understand the compaction mechanisms that are specific to a press-coated tablet.

Please know that this work was published earlier this year, in March, in the International Journal of Pharmaceutics, so don't hesitate to refer to this article to learn more.

[MySTYL'One members access the article HERE


So, I will now present the methods - How did we do our experiments?


So, first, the compaction of the core, of course. We chose 2 model excipients to do our core: first Microcrystalline Cellulose that was mixed with 0.5% Magnesium Stearate and second Monohydrate Lactose that was mixed with 1% of Magnesium Stearate. We chose these two materials because the first one is typical of a ductile fracture and the second one is typical to undergo brittle fracture. So, therefore, we can study both.

Press-coated tablets with STYL'One Evo

Press-coated tablets with STYL'One Evo

The MCC were compacted at 150 mPa's and lactose at 300 mPa's, and both with 8 millimeters round flat punches. Then there's the coating compression, which we did only with MCC and the shell. The coating after one compression was a variated parameter, we made it varied between 25 mega Pascal's and 150 mega Pascal's. So, know that we chose this variable as the main compression force divided by the punch surface which corresponds to a mean axial pressure in the tablet. It will have an importance later.

And of course another parameter that variates is the layer thickness that we set at three levels: 0.6 millimeters, 1 millimeter and 1.8 millimeter and every press-coated tablets were compacted with 60 millimeters around slack punches. So, that was the coating compression.


Then what was of interest is to recover the core after the coating compression. So, the initial core is press-coated with the selected parameters. And then we proceeded to open the press-coated tablet very carefully with a scalpel blade to recover the core without damaging it. And then this is interesting because we can characterize the core before coating compression and after coating compression. Before and after it was characterized in dimensions - diameter and thickness and mass. With this we can calculate the density of the core, initial and recovered after compression. And we also proceeded diametral breaking test to assess the tensile strength,that is the mechanical resistance of the tablet that we calculate with the common formula.

Numerical simulations

Aside from the experiments, it is often interesting to lead numerical simulations. So I will briefly introduce you to the generality of numerical simulation, and then we'll see precisely how it is for our process.


So the principle of numerical simulation is that we have a process or phenomenon that we want to study and we describe it with mathematical formulas into a numerical model that is supposed to reproduce the real process. And then with computer calculations, you can get a response that is close to the reality of your process or phenomenon. This has the purpose to understand and improve the complex processes - as ours - and to have information at lower cost as if you had to do experiments. So let's now see how our numerical simulation of coating compression is.


So we chose the finite element method (FEM) to model this on the software Abaqus. So you see this is a numerical reproduction of the tablet and press. Here the yellow lines represent the punches of the press, in red, it represents the die wall and in blue, it represents the powder - the core and shell. Then the particle corresponding to core and shell tablet is meshed with finite element, which is the principle of FEM method.

FEM numerical simulation of coating compression

FEM numerical simulation of coating compression

And these elements are linked with mechanical properties that are from calibrations that were done on MCC and that will reproduce the behavior of the powder under compression. And then the compression is computer simulated. This has the very high interest of assessing the stress distribution in the compact during simulation and the final density field all over the tablet at the end of the compression. These two variables are quite difficult to assess experimentally, so it is a great advantage to use the numerical simulation. 

Experimental results

Core diameter

So, let's now take a look at the experimental results.


So, first of all, this curve represents the variation of core diameter before and after coating compression at different pressures.

So, first thing we see is that the core diameter increases with the coating compression and with an apparent pressure that is way inferior to the initial compression pressure of the core. As a reminder, our MCC cores were compacted at 150 MPa and here of course, the diameter increases at a very low pressure (like 25 or 50 [Mpas].

Regarding the thickness, it is the opposite effect: the thickness decreases with the apparent pressure of coating compression.


So with this animation, we can see that it's like a flattening effect: the core flattens during coating compression.


And second thing that is stunning that we see on this curve is that the layer thickness influences the proportion of this effect with a thin layer - here marked with the black dots - we have stronger effects of flattening than with a thick layer.


These were the results for MCC cores, but the results for lactose cores were similar. 

These curves represent the variation of density of the core recovered from press-coated tablets compared with the initial state.

And here there is a very stunning effect that is a loss of core density like earlier at very low apparent pressure. In compaction of powders a loss of density is often a sign of partial failure. So, this is quite interesting to note. And this is very, very severe and very clear for the lactose core, here on the right, that are typical to be brittle. And then at higher compression pressure, you see that the density can go higher.

In the case of MCC cores, it can even go higher as the initial state. Here again the layer thickness has a role. It's not a role of making it more severe, but more like a shifting role. Because the effects appear at much lower apparent pressures with thin layers. As the density has varied, it is of course very interesting to look at the mechanical resistance of the core recovered after coating compression. And what we see is that the same trend, same thing, observed: there is first a loss of resistance and then a regain of resistance. And once again, very severe for the brittle cores that are reduced to a very low cohesion. So this quite confirms the partial failure of the core that is very severe for Lactose.

Variation core density after coating compression

Variation of core density after coating compression

Alright, so, we'll now try to explain this experimental results in regard of the numerical simulation.


So, these three figures are the results of numerical simulation lead with the same compression force, but with different layer thicknesses. From up to down there is thin to thick layers.


So, first thing that I want to say is that the colours represent the actual stress - that is the actual pressure that is locally present in every point of the tablet.

So this is why it is important to differentiate from the apparent pressure that is a mean all over the tablet.


First thing we see is that the actual stress is strongly heterogeneous in the tablets during compression and indeed concentrates highly on the core. This effect is all the more important that the layer is thin - see on the figure that is on the top - where the layer is thin: there is more than two times the mean actual pressure that is concentrated on the core.


So this quite explains the different deformations if you have varied the thickness of the layer. So, what I can say regarding this is that if you want to preserve your core, a thick layer should be better.

Density field

There is another field that is important to look at in numerical simulation is the density field. So, here the color represents the more or less dense region after the coating compression. In red it's very dense and in blue - less dense. And here again there is a very heterogeneous density all over the shell which results in a very compacted layer above the core and less compacted band. Again the heterogeneity is stronger with a thin layer.


This is also important regarding the penetration of liquid through the band, when you do a dissolution test, because the penetration will depend on the porosity at every point. And we also can clearly see on the surface of the tablet, the image of the bottom which is SEM image of the surface, where we can clearly see a band with a lot of porosity and the layer with very few porosity. So, please remember that layer thickness is also a critical parameter for the delayed release of press-coated tablets.

Layer thickness is a critical parameter for the delayed release of press-coated tablets
Léo Picart

Another parameter that we studied was the diameter of the core. So to have these effects, we also lead simulation with different core diameters with same layer thickness.

Once again it's the same compression force that is applied in both simulations. And what we see is that with the bigger core, there is a higher core surface to spread the concentration of axial stress which results in quite low axial stress on the core and in the band in the case of the core. And once again it can impact the liquid penetration through the band and of course your lag-time, so the diameter is also to take into account to meet your lag-time needs.

Conclusion of results

Alright, so to conclude, I would like to say that with help of the STYL'One Evo we were able to lead a study that gave a high advance in the field of science first, and as well as being useful to understand the industrial process.


So that the structure of the core is highly modified after the coating compression in terms of resistance and dimension and even if the compression pressure is lower than the initial compression of the core.


So, never consider that your core remains the same after coating compression.


We highlighted that the thickness of the layers and core and shell diameters have a key role in the stress distribution during coating compression. So, they effect the density and mechanical strength of the core, which can have a possible influence on the release profile of the active ingredient. So, this makes both parameters critical parameters, of course, during development and design of press-coated tablets to play on the quality attributes of the final tab-in-tab.


Once again, you can find much more detailed conclusions in the full article, which can which you can go search.

And I would like to finish with to say that my PhD is only halfway to the end, so there is still a lot of work to do and to come. So, we're going to study all the parameters that can have effect on tab-in-tab and performance, like the core centering, the gap between the center of the core and the center of the shell,  also the aging of  the tablets after production and the shape of the tablet, as it can be flat or convex. So stay tuned to learn even more about tab-in-tab, I will let you know.


Thank you to everyone to make this project possible, especially my advisors from University of Bordeaux and SKYEPHARMA and to all the team of SKYEPHARMA. Thank you for listening to my presentation. I will let Bruno conclude this whole presentation.


[Bruno Leclercq – MEDELPHARM]


Thank you, Leo, for your very nice presentation. Very interesting presentation. And I guess the people that are working with tab-in-tab have learned things that they should normally do to look at the robustness of their formulation.

As a kind of conclusion, what we learn is what would be the reason to develop press-coated tablets?


We know there are technologies available like GEOCLOCK. And we also saw an example of commercialized press-coated tablets and the rationale for this technology for that special specific disease. We also learned that STYL'One Evolution is a key technology that will enable you to develop complex oral solid dosage form including obviously the tab-in-tab, thanks to the presentation by Léo and his work during the thesis that geometrical process parameter can be critical for successful tab-in-tab development..


Obviously, stay tuned because Léo will teach us quite a lot in the future that we didn't know which is always exciting. If you ever have some kind of complex formulation, obviously, always good to rely on partners and obviously SKYEPHARMA being an expert in it could be a resource and at MEDELPHARM Science Lab where we are actually located today, we can help you to develop your formulation. 

And if you need more information about the STYL'One technology, feel free to contact us.


I'd like to thank you for listening. And now it will be time for the questions. Aline, Léo myself are ready to answer all your questions. And if the question will answer if we don't, we will let you know. I will leave it to the moderator to start the question and answer session.

Q&A session

[Nick Robertson – BUSINESS REVIEW]

Fantastic. Thanks, Bruno. So guys, as we were saying, we're going to now start the Q&A section. If you do have any questions at all, now would be the best time to just drop them over in the Q&A tab which should be in the top right of your screen. So I'm going to kick things off with the first question:


 "The work was done with flat faced tooling, would you expect similar results with other shapes?"




So, with other shapes, I suppose that you want to say beveled or concave punches. So, I would quite expect similar results, but not in the same extent. This is an ongoing study, so, maybe a further webinar when the results are coming.


[Nick Robertson – BUSINESS REVIEW]

"Do you measure the breaking force of press-coated tablets if you do how?"



Yes in the industrial process, we measure the breaking force of press-coated tablets with the diametrical test - the same for every kind of tablet - but they say this test might be quite limited. In the case of press-coated tablets, this was one of my works that will be soon published, I hope because the diametrical test applied to press-coated tablets is not as simple as for the single tablets.


[Nick Robertson – BUSINESS REVIEW]


How is the choice to be made between three layer and tab-in-tab solutions?


[Aline Moulin   – SKYEPHARMA]


Okay, so, I can take this one, I think it depends on the application, you want to have in the pharmaceutical sector, I will focus on this sector. For the multilayer for example the GEOMATRIX® technology, you will obtain sustained release formulations and sustained release dissolution profiles.
For the tab-in-tab tablets that you will have a lag time and then a pulsated release. So it depends on the performance you want of your tablet.


[Nick Robertson – BUSINESS REVIEW]

"Are you recommending to recover the core during development to assess its properties?"




During development, Yes, totally. Because it can allow you to have an insight of how does your core modified with coating compression: Is it more dense at the end, less dense? We have seen that it can be very different regarding the core material. So, yes, never fail to do this, it will only give you useful information about your process.


[Nick Robertson – BUSINESS REVIEW]

Now, this one is another one about breaking the core and this one reads "How do you know the amount of compression force to apply without breaking the core?"




You can only do it with applying growing compression force and recovering each time the core and see at which pressure does your core break. It depends, once again on the core and on the the shell I suppose.


[Nick Robertson – BUSINESS REVIEW]

So here is another question that's come through "Is the core placed onto the powder bed or is it pushed into it?"



It is first placed on it of course. And then there is either with STYL'One mechanism like a finger push it into the powder bed or with the industrial machine, it is a tamping that is done by the punches. But in each case, there is the core that tamped in the first powder bed.

[Bruno Leclercq – MEDELPHARM]

And this is actually important to position the core in the bed - not only the x and y axis, also in the z axis - to make sure that the core is at the center for the thickness of the tablet.


[Nick Robertson – BUSINESS REVIEW]

So here's another one that's come through this one reads “How do you define large and small inner cores?"



Well, this is relative to the shell diameter. There is no clear definition but only if you have a core that is twice smaller than your shell it is medium it is if it is less, it is small. If it's larger, it is large, there is no clear boundary, but it is relative to the shell diameter.


[Nick Robertson – BUSINESS REVIEW]

"Why did you choose such a large diameter? 16 millimeters is quite large for a tablet?"



Yeah, this is large but this is how you get interesting results. You always have to push the parameters to quite extreme levels to understand fully the phenomenons that occur.


[Nick Robertson – BUSINESS REVIEW]

"Are there tab-in-tab products for which the second layer is a different product than the first layer.


[Aline Moulin   – SKYEPHARMA]

So, yes, that can be done. It depends, for example, if you need to have an immediate release, and also delayed release. So that can be that can be developed. Yes.


[Nick Robertson – BUSINESS REVIEW]


Let's move to the next question. The next one reads, "Is it possible to make small batch tab-in-tab with STYL'One Evo?"


[Bruno Leclercq – MEDELPHARM]

Yes, with the STYL'One, you have the option to use what we call our production module, which will actually allow you to produce small batches - that will also be able to reject the good and the bad tablet. And to record all your parameters during the production.

good/bad tablet sorter with integrated deduster

Good/bad tablet sorter with integrated deduster

[Nick Robertson – BUSINESS REVIEW]

So someone asked "What is the minimum diameter difference between the shell and the core?"


[Bruno Leclercq – MEDELPHARM]

I mean, typically, I mean, that's something that also maybe need to be studied in the future. But typically, we say, you need a minimum of two millimeters at each side of the core. And that seems to be obvious, because if you have not enough distance, on the outside, I mean, the release might be affected. That's why this might be critical.



Of course, if you modify the diameter of core and shell, like the ratio between the two, it strongly affects the lag-time. So it is critical to play on your release attributes.


[Bruno Leclercq – MEDELPHARM]

And also to add something that like we've seen in the study from Léo, is that the way you apply your pressure, the core is changing, the dimensions are changing, the thickness is reducing. If you're too close to the edge you might get problems and maybe variations in your new release profile.


[Nick Robertson – BUSINESS REVIEW]

"What kind of cores can be used in tab-in-tab development? And what are the limitations of certain cores?"


[Bruno Leclercq – MEDELPHARM]

Yeah, I mean, obviously, the limitation in terms of the size of the core, and it will also depend on the size of the outer layer. The other thing is, on the STYL'One we can actually use different kinds of shapes - could be flat faced or kind of concave. And but then you always have to keep in mind that you can do on the STYL'One, but you always have to think about that you will have to move to production and to see what's actually feasible on the production press, and also always to talk to your supplier or tablet press to see if that's actually feasible or not, don't start a project, then realizing that further down the line it's not possible on a production scale.


[Nick Robertson – BUSINESS REVIEW]

Thank you. Now, another one that's just come in. And someone asks, "Is there any other applications other than pharmaceutical ones?"



[Bruno Leclercq – MEDELPHARM]

I mean, we've seen that the way some people looking at developing kind of tab-in-tab, more for kind of marketing reasons to differentiate themselves. Obviously, this is also something that we have seen. We've seen that in the nutritional market to where people also have been looking at tab-in-tab tablet formulations.

[Nick Robertson – BUSINESS REVIEW]

For the pulsated release, for example, three hours delay, what excipient do you suggest to use in the outer layer?"



For the outer layer I suggest an excipient that first must not be soluble, because if it is the shell with dissolve. So, it has to be insoluble, and keep a certain porosity, to allow the media to penetrate through to the shell. And then you can play on the described parameters to play on the porosity in the shell.


[Nick Robertson – BUSINESS REVIEW]

"Do you use polymer matrix on the outer layer?"


[Aline Moulin   – SKYEPHARMA]

Yes, this is the type of metric that is used for the outer shell.


[Nick Robertson – BUSINESS REVIEW]

Fantastic. And now, we're on to the last couple of questions. So, just reminder to the audience, if you do want to ask a question, and we have a few more minutes to answer them. So now would be a fantastic time. But here we are on to the next question. This one reads


"Is the core always centered?



Theoretically, yes, it can then be studied, like how the centering of the core can affect the risk profile. It is ongoing work. I can now say that, yes, it affects strongly. We'll maybe publish it later. We'll see. But theoretically, keep your core centered. It will always be better than uncentered.


[Nick Robertson – BUSINESS REVIEW]

"What would be the influence of coating the core before on its resistance to force?"



I don't know. Like if you coat your core before press-coating, you're doing a double effect. Maybe there is interest, but I can't see it right now. This is something that can be studied [in the future].


[Nick Robertson – BUSINESS REVIEW]

No worries. And so that looks like all the questions we have for today. But what I'll do, I'll just give a short conclusion.


So yes, thank you to all the speakers. Thank you to allow Bruno and Aline for a fantastic presentation.

And also thanks to MEDELPHARM and SKYEPHARMA for sponsoring this session.



Thank you all for coming by.


[Bruno Leclercq – MEDELPHARM]

Thank you for for listening and stay tuned for the next one.


[Aline Moulin   – SKYEPHARMA]

Thanks very much guys.

[End of transcript]

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