Episode 3: Pressurized meter dose inhaler plume characterizations

John Price:

Welcome to coffee with Kindeva, a series of thought-provoking conversations about complex, drug delivery. Today, we’ll be talking with Dr. Ben Myatt at about pressurized meter dose inhaler plume characterizations, specifically around alternative propellant temperature and pressure measurements. Hello, I’m your host John Price. And I’ve got Ben Myatt with me here today. Ben received his doctorate in mechanical engineering from Loughbourgh University, specifically around the fundamental study of the primary atomization mechanism and aerosol plume development of the pressurized meter dose inhaler. Currently Ben works for Kindeva Drug Delivery as an advanced product development engineer. Ben recently presented to talks at the DDL Christmas lecture series in 2020 links to those presentations are available in the description for the podcast. Ben, let’s start out with a brief overview of what you presented at the DDL Christmas lecture.

Ben Myatt:

We did two presentations at DDL. One was looking at the pressure and the temperature of various different formulations fired through inhalers. And that was actually within the inhaler itself in the, sump of the inhaler The sump is a little void or volume below the can, which contains the, the formulation. And just before the orifice that, the plume exits through that the patient would actually see if they look inside the mouthpiece. So the pressure and temperature measurements inside the sump and the second one was around temperature measurements of those plumes when they’re fired into an anatomical mouth throat and anatomical my throat. He’s a model case that we use for  for testing in the lab a representative model of human airways. So it’s got an oral cavity and then into this kind of laryngeal pharynx in the region of the actual throat  itself.

John Price:

Yeah.  there is a picture of it in, in your presentation, it looks like a plastic throat laying on your, your work bench.

Ben Myatt:

Yeah, so it’s, it’s, it’s based on it’s based on a real human is throats. So it’s an MRI image that was taken over humans, and it’s been then turned into this throat geometry that we can use in the lab. It’s widely used by it it’s freely available and widely used throat geometry. What we’ve done is we’ve taken that geometry and instrumented with thermocouples. So we’ve added little holes into it, kind of create an outer shell from that kind of internal skin geometry, or just the, that we 3D printed ourselves and then done the measurements.

John Price:

Okay. so maybe help me just get a better understanding of kind of maybe the basic components of these pMDIs, you know, your, your standard inhaler. I know they’re not all the same. They’re, they’re certainly, you know, other types of inhalers out there, dry powder inhalers. And, and what we’re specifically talking about here are the, the pMDIs.

Ben Myatt:

So start, the start is at the heart of the inhaler. We have what we call the can closure system that consists of the canister, which holds the reservoir, which holds the formulation and a metering valve, which performs the function of every time you depress this, can it meters out a very precise and a small volume of liquid, which is the dose that you then receive inside that can, and the valve is the formulation that consists of the liquified propellant gas at pressure, and also the active pharmaceutical ingredient. We call it the API or the drug. Sometimes the API is suspended in that propellant, and sometimes it’s dissolved in a cosolvent quite often is ethanol. And that’s contained in the propellant in a solution to kind of got those two different formulation systems and then surrounding the whole of that container closure system, surrounding that canister is your plastic actuator body. That’s generally the colorful bit as you depress your can and the metering valve emits your dose. It kind of the dose travels through the little white plastic stem or sometimes a metal stem into the actuator body through a series of passages and then out for the final orifice, the exit poll that when you look into the mouth piece, you’ll see a little black dot generally, and that’s the orifice that the spray plum comes out of. So you’ve got a can inside a plastic actuator. Sometimes we have some additional components. There’ll be a dose counter for instance, in there and that, or an indicator. And that will either tell you kind of roughly how many doses you’ve got inside that device, if it’s an indicator or exactly how many doses you’ve got inside the device, if it’s a dose counter.

John Price:

Okay. Okay. That’s a, yeah, that’s helpful. Can I get a picture in my mind? Why is like your, your papers that DDL talk, you know, are really on, on pressure and temperature? Why are the, why are pressure and temperature of propellants so vital for proper pMDI delivery? What, what is it about the pressure and temperature that begs to be measured in, in a way that you’re doing?

Ben Myatt:

So the pressure particularly is the driving force behind atomization. There’s kind of two schools of thought about how droplets are actually made by an inhaler. That’s an air blast type atomization, or it’s a flash type atomization. And it’s probably a hybrid of both of those that, that the actual mechanism by droplets are produced pressure drives both of those mechanisms though. So that’s either pressure to force your liquid and vapor formulation out of the inhaler, or it’s the pressure basically because you’re holding that gas at a a higher pressure because of your ambient temperature and that when you release it it kind of explodes essentially flash boils quite rapidly and violently to produce these small droplets. So realistically the higher, the pressure, the finer, the droplets that you, you kind of produce from your device, it’s the driving force behind the atomization. It also influences the speed at which the plume comes out the higher, the pressure, the faster, the plume, normally as well, but obviously that’s also kind of a function of the device hardware. So that’s kind of the defined exit orifice diameter of your pMDI. And this is one of the factors that also influence the kind of droplet sizes as well as kind of surface tension viscosity of the formulation and that kind of, you know, it is a result of the, the propellant that you choose. And also if there’s other excipients or co solvents. So the chemicals that we’ve added in to that particular formulation to, to help make that final product, but really it’s the pressure that drives the atomization process. And the temperature is it’s kind of a fundamental property of the propellant that you you kind of, they go hand in hand the pressure and the temperature. I mean, the temperature is around the boiling points and that’s kind of the other property that we talk about the boiling point of this this liquified gas, and they’re generally quite cold, you know, they’re below zero degrees centigrade.

John Price:

Okay. Okay. So how do APIs and propellants kind of coexist did they express themselves differently in the activation plume? You know, you’ve got, you’re, you’re talking about kind of this liquified gas, you know, you’ve got solovents sometimes these, these co solvents, or do they, they float around in there, is that why I have to shake it up? Is it just the drug is, you know, generally well dispersed within that canister, you know what, you know, each dose is like, here’s a little bit of the API, here’s, here’s a little bit of propellant. And does the mixing there, you know, just some, how, how does that mechanism work within the pMDI?

Ben Myatt:

Yeah, so we have two different types of formulation kind of paradigms if you like, one would be a solution formulation, and that’s where we have the ethanol. And it did the drug or the API is dissolved in that ethanol. And that ethanol is kind of makes up a percentage of the dose that you’d receive and the remainder would be your propellant. So every time you, you depress the, can you get like a, you get a homogeneous solution that is dispensed through the valve and then into the, the atmosphere suspensions are the other paradigm and they are physically drug crystals or particles that are suspended. Hence the name in the propellant pretty much, you know, for, for both cases, you want to shake your inhaler and to make sure that everything is well mixed, but that’s really, really important for the suspension formulations, because you need to make sure that the drug that’s in that propellant is all homogeneously mixed and well distributed and suspended. And so next time you press the can down and take your dose when you release the canister that’s actually, when he takes the next dose into the metering chamber. So it’s at the end of that, the spray event that you’re preparing your inhaler for the next time you’re going to use it. So if you haven’t, well-mixed the inhaler, the formulation inside the inhaler, then you might get inconsistent dosing next time you use it. That’s why shaking you so important.

John Price:

Okay. so that, that kind of leads me to my, my next question, which is, you know, again, some of these might be, you know, me coming from, from my viewpoint, but, you know, I shake up my inhaler and I’ve always wondered, you know, what is that shaking up in there? You know, it seems like water, but you know, now that I’m in the industry, I know that’s not all API in there, but I guess that shaking is, is the, the liquified propellant is what I’m hearing, because I’m like, well, liquids not fall out, you know, come shooting out of here. It’s pretty much just the vapor and gas. So I’ve always kind of wondered when I was shaking that, is that what I’m feeling when I shake that canister?

Ben Myatt:

Yeah, absolutely. It’s that liquified propellant gas with the API and any other co solvents in it when we have a suspension formulation, one of the other factors that play around this kind of shaking action is around how the API kind of behaves and, and that kind of is around its morphology. So did the drug particle size you know, depending on what the drug is, we might have quite a small particle size. You might have quite a large particle size. Is it very dense? Is it heavy? You could particle engineer. So you can actually create drug particles that are hollow they’re very light. So they might be big, but actually they have a low mass and sort of have like an aerodynamic particle size is quite small and equivalent particle size, but one that’s related to the aerodynamics of the, the, the situation. And there’s also about the powder loading, the amount of drugs that we put in there as well. So if you’ve got a lot of powder, you want to make sure it’s dispersed, that’s why you shake it.

John Price:

So, you know, I know there’s different ways to basically put this formulation into the canister and, you know, I’ve, I’ve heard pressure filling and cold filling. Why would one person cold fill or pressure fill? Are there benefits or is it strictly to do with the API? Why, why would you choose one over the other?

Ben Myatt:

So there’s kind of the two ways that you’ve just mentioned John, this cold filling and pressure filling cold filling is kind of, as you, as you’ve, you’ve identified, it’s a cold process. It is a process where we take a vessel. We chill it down to below the boiling point of the propellants and we, we add that propellant in. So it stays in its liquid state. So everything is a cold state and we add in the drug or the API, we mix it all up quite, you know, really, thoroughly. And then we essentially decant it under gravity. So it’s like a little tap, essentially an automated process to, to count the known amounts or the particular amount into each little canister. We then take the canister, put a valve on top of it and we crimp it. And that then gives you a the final can, which has then warmed up to. It’s kind of our ambient temperature. And that’s the point at which this, this liquified gas you know, takes on a pressure because it’s a warmer temperature.

John Price:

Yep. since it’s in a sealed environment, went in cold, but now you’ve sealed it. And as it warms up, it creates that pressure in the, okay. That, that makes sense. So with pressure filling, why would you do a, like a pressure filled type?

Ben Myatt:

So pressure filling basically consists of taking a, can you put the valve straight on top of it, you crimp it, and then you fill the formulation through the top, through the valve. So you fill it under pressure. That’s what you have to, that’s where the pressure comes from. Sometimes some of the non-volatiles or as we call them, or that the excipients could be added into the can in advance. And then the valve is crimped on top, and then you fill the propellants in. But most, most normally the, the formulation is made up in a vessel and is then injected into the can at pressure. The differences are kind of based on what manufacturing capability a given company might have there’s pros and cons to both pressure filling, you are operating at ambient temperatures, but you have to have highly pressure rated equipment because the pressures are involved you know, a higher pressure set pressure filling could be advantageous for materials or API use that are temperature sensitive because you don’t have to undergo this cold chilling process, however, cold filling disadvantage that you have to use energy to obviously chill that vessel down. But your advantage is you’re not operating at such a high pressure, not pressure at all. One of the advantages for cold filling would be that you perhaps can fill high powder loading formulation. So formulations that have a, a lot of drug in them and a high powder loading, we call them you could fill them perhaps a little easier and more consistently are better than, than pressure-filled formulations. And that’s just due to the fact that you’re trying to squeeze so much drug backwards through the valve, essentially. If you’re a pressure filling here, whereas cold filling, obviously you’re pouring into the top of the open can and then putting the valve on afterwards.

John Price:

It reminds me this isn’t the first time that, that we’ve, we’ve gone through this. So if I’m remembering correctly, these inhalers pMDIs used to be filled with CFCs, we transitioned away from the CFCs to HFAs. And I guess I’m wondering if you could talk a little bit about the history of, of moving, and I know you’re, you know, you’re a young man, this may predate you, but I’m guessing you’ve, you’ve at least studied about the transition before. So if you talk to me a little bit about the transition from CFCs to HFAs.

Ben Myatt:

Yeah. So, so CFCs or chlorofluorocarbons were the norm for the refrigerant. Sometimes you call them f-gasses or propellant gasses in our case really widely used. And in the 1980s, late eighties, there was research that showed that these gases in the release of these gases, into the atmosphere, particularly the stratosphere caused ozone depletion. And so the Montreal protocol was signed. And as a result of that, there was an agreement to phase out the use of CFCs and HFAs hydrofluoric alkanes with the kind of chosen alternative propellant, gasses at that time. And so a lot of work went in, in the early nineties, early mid nineties through to even the two thousands to, to develop products that used HFAs instead of CFCs. And obviously there are differences in properties between the CFC propellant gases and the HFA propellant gases, and that led to some differences in the product performance. They’re kind of two different ways you could go about that process. One was to try and make an exact match of the, the, the product so that your patients saw no difference. And that was essentially making you an equivalent product. When you do switch out the gas. The other one was to make use of the fact that HFA gases actually were kind of higher pressure gases. And so you actually make more efficient products. And so there was a step change in efficiency of some products and, you know, regulatory pathways of getting products approved, kind of created those two different avenues for product development at that time.

John Price:

Okay. So a similar type transition going on.

Ben Myatt:

So today the kind of the global focus is around being green on carbon footprints. And I, I, current HFA propellants don’t have a great global warming potential. And that’s the, the, the kind of relative impact to the environment of say compared to CO2 recently, there was an amendment to the Montreal protocol and it’s called the Kigali amendment, which is to phase down the use of our current HFA propellants with a view to replacing them with lower global warming potential propellants. So we could say that we are kind of going through a similar development in the industry that we did when we went from CFCs to HFAs. And it’s the next generation of propellants now there’s another HFA 152, and there’s also HFO, which is a hydrofluoroolefin 1234 And these are being looked at by various players in the industry as alternatives to our current propellants. But of course we don’t know much about using those propellants in inhalers yet that work hasn’t been done. So this is what we’re starting to do this work now.

John Price:

That’s great. That kind of brings us back to the, some of the work you you’ve been doing, because if we look at your presentations from there, you’re, you’re not just modeling a propellant through the, through these models, but you’re, you’re actually testing a variety of different propellants. Is that correct?

Ben Myatt:

Yes. Yeah. So we we’ve been doing some work with, with these new two candidate propellants and comparing them against our current two propellants the de rigueur in industry. Yeah. To try and understand more about the differences and the similarities between, you know, the new and the current propellants. You know, and there’s a number of different ways we can do that testing there’s, there’s the kind of standard pharma testing that we do. And there’s also some other fundamental tests that we can do to understand more about the nature of, of the pMDI propellant systems. So the, the, the, these new propellants in pMDI, how does it behave? You know, and that’s going to help steer development of new products, because when we have that fundamental knowledge about how these new propellants behave, we can make more informed decisions during our product development. We can hopefully, you know, speed that process up. We can get to a clinic quicker because we’ve got that background knowledge and that couples with the knowledge that we have from our kind of day-to-day process of developing new pMDI products you know, bring our background knowledge with our kind of research into these new propellants together. And it puts us in a good, good position.

John Price:

Okay. So, so from a customer standpoint, they, you know, we’re, we’re basically, you know, doing some of the legwork that that’s going to have to be done. And this is the beginning stages of, of some of that testing that, that we’re trying to get ahead of here. So we can be ready for our customers and, and, and continue to produce these medicines for, for the patient.

Ben Myatt:

Yeah, yeah, absolutely. It’s trying to identify some of the issues that we might face later in the development process, but upfront. So with this fundamental knowledge that we will have, we’re kind of out, you know, we are better equipped to develop products you know, with a better, better chance of success. And again, you steer our R&D work in the future, as well as kind of, you know, we know we know where the areas that we’ll need to work in for a given product opportunity.

John Price:

So what exactly is it that you’re looking for in a new propellant?

Ben Myatt:

So ideally we’d like a propellant that has similar properties to the ones we currently use, because that will make the switching process or adopting these new propellants in, in new products, easier some of the key parameters. I guess, if you want to, you know, label them would be there’s pressure of the vapor pressure of the, of the gas or the propellant, there’s the boiling point, the temperature at which he boils there is the density and that kind of, some of the big key ones, sort of the key parameters that we want to, we’d like to try and you know, keep similar this physcio-chemical properties we call them. And even the thermodynamic properties, we’d all like them to be similar because any differences are going to mean that we have to re-engineer the device or the formulation to kind of account for them and to try. And, you know, if we want to try and bring it back to a kind of very similar product to what we may have developed in the past going forward, which we kind of have to make those those changes to, to account for, for any differences in the propellant, this is kind of why it’s so important to have something similar in the first place at the end of the day, the biggest thing we’re trying to do here, he’s trying to get drug into the lung of a patient. And so, you know, I talked here earlier on about the temperature and the pressure of that propellant being really important into the atomization process. Well, that atomization is generating droplets that are going to convey the, the API or the drug into a person’s lung. And so obviously, you know, similarity and pressure and temperature they’re important there. Because at the end of the day, we’re trying to make a product that still gets drug into the lungs for the patients. Alternatively, we could harness some of the advantages of these new propellants to try and improve the efficiency of the inhaler or the pMDI in the future. And that’s one of the areas of my main focus. Additionally, the other difference we might find is around chemical stability and manufacturability of the product. So we still got to be able to make a product, having it with a usable shelf life without huge of any degradation, I’ll be the safety or performance.

John Price:

So in, in your, your paper, in this specifically around the model that was used, you talked to me a little bit about this model you know, why how does this help really understand these, these temperature and pressure things? You know, I know, you know, it’s a, it’s a model of, of the throat, but what I guess, what did you do specifically within the model to help measure these, these differences in temperature and pressure?

Ben Myatt:

So, in, in our lab testing, that’s the routine lab testing that we do, and the other companies do we use throat models, to take the spray that we generate from an inhaler and into our test equipment. They’re an interface if you like the test equipment and it’s become much more widely used now in industry we use anatomical throats. They’re more realistic to an anatomical human geometry. And so we get closer results to those that we would see in, in vitro in the lab against, in vivo in a clinic, some work was done in the two thousands by they were called the OPC consortium, which is a consortium of a few different pharma players. And they did MRI scans of humans, I think around 20 different humans. They did MRI scans of humans. Those scans that have been developed into test apparatus, and there’s a medium and a small and a large geometry that are available to industry for purchase and use in testing. We have taken the medium throat geometry and developed our own kind of in-house design and produced and manufactured an instrumented version of this, which includes small holes that we then pass them a couples into the, the oral cavity in the throat region. So that when we fire an inhaler into the throat geometry, we can measure the temperature of that plume. And we can track it through the patient’s kind of oral cavity and into the throat, and then out to the device. And that was 3D printed with our own capability in house and the aim is to obviously to measure what the patient might feel, what the patient might experience by taking these products.

John Price:

So when that, when the plume comes out of the end of the, the inhaler, how fast is it actually moving?

Ben Myatt:

So we’re looking at measurements at the mouth piece exit of 20 to 30 meters, a second depending on the exact configuration of the device and the propellant that we’ve used. And, and that’s kind of roughly 40 to 50, maybe even 60 miles an hour to give you some idea. I was really interesting because we found that during the CFC to HFA transition my mentor I, one of our company’s scientists Steve Stein did a lot of work around he also measured pressure temperature, and also the force of CFC and then HFA spray plumes, and they found that the CFC plumes they, they, they called it the cold Freon effect it was found. And that was basically, it was a really cold, forceful blast of propellant and liquid impacted in the the mouth and the throat. And it had to kind of get either two things that happened. It kind of could, could cause a patient to stop inhaling their medication properly. So that meant that they didn’t get any proper dose. But then when we moved to the HFA transition plumes and moved to HFA plumes, they were much warmer. And if we transition to new propellants, what will that look like?

John Price:

Great. Yeah. So around that temperature piece, I, you know, I guess I’m, I was surprised to see how low the temperatures get, you know, if, you know, I’m guessing it’s a very short phenomenon, so, well, it will make it close to freezing. It’s very, the timeframe is so short that, yeah, it can feel a little, a little bit of a drop of temperature, but, you know, since the rest of my mouth is 98 degrees you know, quickly warms up as it makes its way, is that kind of what happens in the plume? And then that kind of leads me to, to wonder, you know, when you’re measuring these, what’s kind of the fidelity of that measurement, you know, what are the, the time increments, you know, is it, you know, it’s think of it, like video would be, you know, how many frames per second, but you know, how many measurements are we kind of taking per second? Is that, is that kind of a way to measure that resolution? Is that

Ben Myatt:

The fidelity of the measurements we, we data log at one kilo Hertz. So that’s every millisecond, the reaction time of the thermocouples where we’ve chosen the kind of the finest thermocouples that we can reasonably get into this into this model. So they are very fast response, but they have to have a time lag, you know this the order of it, you know, a few milliseconds to kind of react to the temperature, changes around them. And that’s yeah, pretty fast for thermocouples yes. The time check the time duration over which the patient feels this temperature is very small. It’s very short. Yes. That’s true. The temperatures that the plume gets down to yes, very cold. Also good point. And again, we know that’s been measured in that being seen for inhalers.

John Price:

That kind of leads me to the question about the tongue, kind of the, does that affect the temperature, you know, and is that part of the modeling that’s taking place or again, is that kind of a negligible effect and can be ignored for the purpose of the model in measuring temperature?

Ben Myatt:

The tounge itself is, is an interesting point, and that’s actually an important point as well, because when you look at someone’s mouth or when you look at them, the front of their face and into their mouth, the first thing you see when they open their mouth is their tongue. And it’s the first thing that is in line of sight for an inhaler when you acutate your, your inhaler. So yeah, we, we found, we found that the temperature of the tongue is quite an important place to, to make this measurement because it’s where that the patient first can interact with the plume. And we find that for some of the propellants the temperature was really low, but for others, it wasn’t so low. So yeah, the shape and the location of tongue are very representative because they come from that, that data from the human, the MRI scans of humans There are some differences, you know, we’re talking of a throat model or throat that is 3D printed, as opposed to you know, human tissue. And so, you know, that will have an impact in the measurements we make. However, the biggest importance with these measurements is really about the plume temperature. It’s the effect that the plume then has on the oral cavity throat. And so when we changed the propellant, if that causes, you know, significant differences in what the patient might feel, and that’s the new propellants might be, if they are significantly different to the old propellants, then that might have the same kind of cold Freon effects that we’re seeing when we went from CFCs to HFAs or they might be in reverse, you know, this is all about trying to understand are there going to be differences for the patient.

John Price:

So even though this is a model you know, plastic model and not human tissue, I I’m guessing since we’ve measured and benchmarked you know, previous temperatures and plumes coming through really what we’re trying to do. And we know those work in human tissues, the, the assumption made is that they will, you know, if we can match this in, in the lab, then once we move into humans, the, the effect should be similar. You know, of course all this is, you know, prone to testing and why testing so important as we move through there. So another question around the model is, you know, how was the dose actually delivered? Do you know, is the, the inhaler like stuck into the mouth? Is there a vacuum draw at the end of the thing, does the model have to, you know, is it actually held vertically? So in case there’s effect from gravity, or

Ben Myatt:

We do draw through an airflow, we use 30 liters a minute, which is pretty standard. It’s kind of, we call it a compendial pharmaceutical testing. It’s what we use for other, other types of pharma measurements. So it’s comparable in that respect. And he’s kind of like, you know, there’s, there’s a wide range of human inhalation maneuvers. So we use, we kind of keep it a little bit more simple, a standard constant flow rate. How do we fire in a lab? Well, yes, we have an adapter that goes on the front of this this throat model. And that’s kind of representative of where your lips and your teeth would be, for instance, and in the center of that is a hole that the, our inhaler test inhaler slot straight into. And then I set the data logger running. I have the airflow on constant, and then I depress the inhaler myself in a press, press and breathe fashion the same way you take your inhaler. Although I’m firing it into the device and not into my own mouth.

John Price:

You know, really the, the findings from, from this research that you’ve done, what, what is, you know, we’ve talked a little bit about the impact and really what you’re trying to model, but what’s the ultimate hope? What are the findings that come out of this study that you’ve done? And then maybe after that, what are some of the next steps? You know, what do we, where do we go from here?

Ben Myatt:

Yeah. So some of this work is, is fairly early stages. And you know, the work that we’ve done is established a broad understanding and the work that we’re doing so far thing with placebo propellants. So that is just the propellant in the inhaler on it’s own, no drug, no other co solvents. So we want to for starters, you know, we’ve done that work and we want to now start comparing it against the, the routine pharma testing. So that’s the kind of cascading factor testing that we do in the lab to determine particle size distributions. And then when we can, you know, we want to compare against current and new potential products. So the new formulations, new propellants in those formulations, how did they perform compared to the the, the, the current products that we have with the older current propellants and then kind of tie that in with the temperature measurements. And there’s some pressure temperature measurements that we also talked about. I want to try and tie all that, bring the story together, paint a big picture, you know, going forward, we’ll do more work with specific formulations. So I started to have more of a co solvents or excipients and drugs in, you know, to, to investigate the impact of actually the drug in that formulation as well. And we’ll also go on to do further work, to investigate how changing the hardware. So that might be changing the valve volume. How much is each, each shot, how much the, you know, the amount of liquid is in each shot. We might change actually to orifice size. So we might have a smaller hole try and make a finer plume. We might have a larger hole that makes it a less fine or a coarser plume. So that’s kind of some of the work we’ll be doing going forwards.

John Price:

And last question here for you, Ben, I’m hoping you can maybe comment on the use of pMDI inhalers to treat systemic issues versus just always a respiratory issues.

Ben Myatt:

So apart from the changes that are going on in the industry at the moment, looking at new propellants and efforts to reduce the carbon footprint of inhalers, I think one of my desires and our desires at Kindeva in R&D is really to push the envelope of, of, of what a pMDI can achieve the performance that we can achieve with it and what it might be used for. And we know what’s possible that might be looking into larger molecules systemic delivery for, for non-asthma non-COPD treatments. And an example of that is the recent announcement that Kindeva has partnered with BOL pharma to investigate feasibility of delivery of inhaled inhaled cannabinoids. We want to know, can we push the boundaries to deliver more drug material more efficiently to more people and for the treatment of more conditions,

John Price:

Ben, I really appreciate your time here today. And from enlightening us all about pMDIs. I look forward to hearing from you again, soon as you develop more new data.

Ben Myatt:

No problem. Good to talk to you, John, thank you

John Price

To that point. I should mention that you will be presenting some of that new data at the upcoming respiratory drug delivery conference in May. Thank you for listening to coffee with Kindeva, a series of thought provoking conversations about complex drug delivery.