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Interview / Presentation with Beatriz Pereira, University of Central Lancashire, for JakajimaTV hosted by Pieter Hermans.


Current healthcare follows an ‘one size fits all’ approach, and it is associated with high variations in treatment outcomes, due to the high interindividual variability. The introduction of genetic and molecular diagnostics for individualised drug treatments has replaced the traditional symptom-centred approach with a patient-centred approach.

3D Printing offers the possibility to 'create' these personalised tablets

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Tech
Transcript
00:08Welcome back at Yagahima TV, today we're going to talk about personalized medicine.
00:13As you know, when you take a tablet, then the tablet is being produced on large scale
00:20and is not, let's say, personalized to your personal situation.
00:25And today I'm going to talk with Beatrice Pereira, she did a PhD research project at the University of Central
00:32Lancashire in the UK
00:34about 3D printing of modular polypills for personalized therapy.
00:38So welcome, Beatrice.
00:41Let's start with what you have been doing on your research project and then we go from there.
00:47Okay, so I'm going to share my screen.
00:51First of all, I would like to thank you for inviting me for this interview.
00:59So I'm going to talk about 3D printing of modular polypills for personalized medicine.
01:03So just a quick overview of my background.
01:08As Peter said, I did my PhD in the University of Central Lancashire, which is in Preston, UK.
01:15And I was part of a research team led by Dr. Mohamed Alnan, who is a pioneer in this field.
01:21So initially I was an Erasmus student when I first came to the UK.
01:25And I worked also in the same uni with 3D printing of medicines in general.
01:30And then during my PhD, I focused more in polypills, which are tablets or capsules with multiple drugs.
01:36So just a quick overview, introduction.
01:41So the current healthcare is based on a one size fits all approach.
01:46And this is associated with variations in health outcomes.
01:50And this is due to the individual variations.
01:53So with the introduction of genetic diagnosis, this approach has been replaced by a patient-centered approach.
02:03So it is believed that in the future, the healthcare system will have a database with information about the patients.
02:12For example, in terms of their genetics, other conditions they may have, their weight, age.
02:18And then this will simulate the target pharmacokinetic profile of the drugs.
02:24And then they will generate an individualized therapy for this patient.
02:29And then this will be, we will have an e-prescription and healthcare professionals will be able to 3D print
02:38these medicines on demand.
02:40So one of the applications of 3D printing more specifically is in the production of polypills, like I said.
02:49And the advantages of this is that, for example, with traditional tableting, we need to produce in large scale.
02:57And there have been many studies studying, comparing the polypills with usual care, which is the administration of several drugs
03:06at the same time.
03:07And actually, they have shown that there's improved patient adherence.
03:10And this is a problem with when people need to take several medicines.
03:14Sometimes they don't take it for one day or two.
03:16And this is associated with disease progression, for example, and increased hospitalizations.
03:22So one of the issues with the traditional tableting methods is the rigid nature.
03:27So, for example, if we have one tablet with three or four drugs that are specific and they have a
03:33specific dose, not everyone can take this specific tablet.
03:38And with the traditional manufacturing methods, it's hard to change just one of the drugs.
03:43For example, the dose of one of the drugs or the number of drugs.
03:46So 3D printing offers much more flexibility in terms of the number of drugs we can add, the dose of
03:53each drug, and we can individualize also the release profile, also improving patient's adherence.
04:01So one of the projects I worked with during my PhD was in the production of multi-compartment capsules.
04:08The reason why I chose capsules was because the technique I used was fused deposition modeling, 3D printing, and this
04:15is associated.
04:17So for this, you need heat to 3D print.
04:21And this can be associated with drug degradation if you melt filaments that contain drugs, and this can degrade some
04:29drugs.
04:30So when using capsules, this capsule will have a shell that will be blank.
04:35So this will be just polymer.
04:38And then the drugs are manually dispensed in these compartments.
04:43So in this case, my goal was to develop two different systems.
04:48And these systems will differ in the design.
04:51So here you can see they have different design.
04:53Here is parallel, here is concentric.
04:55And they will also differ in terms of the polymer that we use.
04:59So on the left, we use PLA, which is not soluble in water.
05:03So the goal here is that the shell will remain intact.
05:08And then the drugs will dissolve through these free pass corridors and through these pores here.
05:15So to show that this is a modular system, I tried different, for example, pore sizes to see how this
05:22was going to affect the release profile.
05:24So I'm going to show you these results later.
05:26Then here on the right, I used PVA, which is water soluble.
05:31So the goal here is that the shell will dissolve with time.
05:35And then I change the thickness of this wall here, the internal wall.
05:42So by changing the thickness, increasing the thickness, I will delay the release profile, the release of these two drugs
05:49that are here in the internal compartments.
05:53So here is a quick summary of how I produce these.
05:59So as I said, I just use 3D printing to produce the shells.
06:04So initially I 3D print the bottom shells.
06:07Then I fill this paste with the drugs.
06:11So this was something also that we optimize this kind of paste.
06:15So we made this hot paste that is easy to dispense with the syringe.
06:20And then at room temperature, it will solidify and it will produce a stable structure and there's no leakage.
06:28Then after this, we just bring the top shell and seal the capsule.
06:35So just really quickly, I will show you more or less how it worked.
06:40So here, as I said, I changed the size of these pores.
06:43So this is the size of the pores here.
06:46So you can see that by increasing the size of the pores, the release profile is faster.
06:54Then with this system, as I said, we increased the wall thickness and this delayed the release profile of the
07:04drugs.
07:05So we achieved what we wanted to achieve.
07:08So we can change the release profile of drugs.
07:11So even these drugs, not all have the same release profile.
07:14We can individualize them just by a digital approach.
07:18So if something is it can be used for a complex therapy, but we use a few starting materials and
07:26we use a easy approach, easy way to do this.
07:29So it's easy for the health care professionals to do it in the future.
07:34And here in this case, I used for specific drugs, but the number of drugs that can be used here
07:39is unlimited.
07:43So I would just like to highlight some of the challenge and future work that needs to be done here
07:48just to apply this in a clinical setting.
07:50So we need to ensure the quality and safety of the drug product.
07:54This is by controlling the formulation we are going to use.
07:57We need to make sure that the components are compatible between themselves and then also between the formulation and then
08:05the equipment with, for example, with the 3D printers.
08:08We also need to control the process. We need to make sure that these 3D printers are GMP qualified.
08:14Also in terms of validation of the control, sorry, validation of the cleaning process to make sure there's no contamination,
08:20cross contamination.
08:21Then there's also the need of more preclinical and clinical studies, clinical studies, especially in populations that may benefit the
08:29most of this, which are, which are pediatric and geriatric populations and see how really they can, how we can
08:38improve their therapy.
08:39And then there's also the need of better regulatory guidance. And so for this is needed that academia, industry and
08:47regulatory bodies collaborate with each other to give us a more specific regulatory guidance in terms of 3D printed drug
08:57products.
08:59So this is it really.
09:01Okay. Well, thank you very much for your, for your, in a very short time to explain your approach.
09:08I have one question, because if you have multiple drugs in one pill, is there no, let's say, how do
09:15you say, interaction between those drugs possible or when people are so have swallowed it that something happens?
09:23It can be. So this is, for example, another advantage of capsules that we use different compartments.
09:28So we physically separate them. So there's no physical interaction between them.
09:33And then, for example, if the interaction between the drugs is, for example, after they are taken, for example, in
09:39terms of pharmacokinetics of the absorption of these drugs,
09:43we can change the release profile of these two drugs.
09:47So we can choose one to release immediately and one to release later to avoid any interaction.
09:52Okay. Okay. Okay. Well, well, thank you very much for this concise explanation about 3D Prima printing and your, your
10:01research project.
10:03As you know, I always ask at the end of the presentation, a personal question and about your favorite music
10:11or art or food or city.
10:13So please go ahead. What's your favorite thing?
10:17I'm going to talk about foods.
10:19I'm Portuguese and I was recently in Portugal.
10:21So I had the chance to eat some of my favorite foods.
10:24I'm going to talk about a specific dish.
10:27I will even share a picture of this, this dish.
10:33So you can have a better idea how it looks like.
10:38Yeah, you make the, what you are hungry then in that case.
10:42Yeah.
10:45So this dish is called francisinha.
10:48And the literal translation is little Frenchy.
10:51This is because the person that invented this dish was Portuguese and used to live in France.
10:56And when he came back to Portugal, he wanted to adapt a French toast that they had there.
11:02It was with ham and cheese.
11:04And when he came to Portugal, they increased the amount of cheese they use.
11:08So they changed a little bit.
11:09And that's why the name is little Frenchy.
11:11Okay.
11:12So this is, I don't, I don't, don't suggest this to vegan, vegan or vegetarians because it contains a lot
11:22of meat.
11:23So it contains Parma ham, steak, sausage, any type of meat you can think about.
11:30And then it has, on top it has a melted cheese.
11:34And then one of the most special things about this is the sauce.
11:39So each restaurant has their own recipe.
11:42In general, the ingredients are the same.
11:44It contains beer, tomato sauce, stock.
11:48But then every restaurant has their special touch.
11:54And it's really, really good, but very caloric.
11:57And it's traditional from Porto, the city of Porto in Portugal.
12:01Okay.
12:02Well, that sounds, it looks very tasty.
12:05So I want to eat.
12:09So, so thank you very much for, for sharing your, your work, your research project and your favorite food in
12:15this case.
12:16And I look forward to listen to your presentation at our conference.
12:22Beginning of next year.
12:23So thank you very much.
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