10 - Formulation and Drug Delivery Basics (S1E10)

All right, get ready, because today, we're diving
deep into drug formulation and delivery. Oh,
this is a good one. Right. It's like you swallow
a pill and just kind of assume, well, it just
works, right? Yeah, you don't think about all
that goes into getting it to actually work. But
turns out, getting that medicine from the lab,
like a scientist's bench, all the way into your
system so it can actually do something, it's
way more complicated. Way more. It's definitely
not just like grinding something up and throwing
it in a capsule. No. Not at all. It's pretty
fascinating, actually. So in this deep dive,
we're going to uncover this hidden world of drug
formulation and delivery. Yes, we are. And it
really is this crucial step between that lab
discovery and a treatment that you take that
actually makes you better. Yeah, I think of it
kind of like, you know, you can have the most
talented musician in the world. OK. But if they
don't have the right instrument or their sound
system isn't set up correctly. They can't share
their music. Exactly. They can't share their
music. I love that analogy. So we have some sources
for this deep dive. We have a textbook about
pharmaceutical product development. OK. And then
we also have a chapter focusing specifically
on pharmacokinetics. Nice. And I think what's
interesting here is that both of them emphasize
this one major goal that scientists have. What's
that? Which is getting that active ingredient,
that essential drug molecule, to the right place
in your body at the right concentration and for
the right amount of time. Right and they're the
scientists are trying to do this right and how
they achieve it really depends on the delivery
method Okay, like we all know pills we know injections,
but have you ever stopped to think why? Some
medications come in one form versus the other
I really haven't actually. Yeah, it turns out
that the delivery method has a huge impact on
how much of the drug actually gets into your
system. Okay. And this is what's called bioavailability.
Bioavailability. So is that kind of why sometimes
I feel like when I take a medication, it's like,
is this thing even working? Yes. That's exactly
why. So think about it this way. When you swallow
a pill, it has to survive a lot, right? It's
got to survive your stomach acid, those digestive
enzymes. Yeah, your whole digestive system. Exactly.
Before it can even be absorbed into your bloodstream.
Whereas an injection kind of bypasses all of
that, right? Delivers the drug directly into
your circulation. Oh, so it's more direct. So
with an intravenous injection, you're getting
100 % bioavailability. Wow. Meaning the entire
dose is getting into your system. That makes
a lot of sense. You know, needles aren't always
the most practical or comfortable option, right?
Right, yeah, needles, yeah, no thanks. But oral
medications, you know, they win for convenience
and patient ease, for sure. They do. But they
present challenges when it comes to formulation
because of that whole complex journey through
the digestive system. Yeah, I can see how that
would be tricky. Yeah. Well, the textbook actually
highlighted a really interesting example of this.
Oh, what's that? They were talking about an antifungal
medication called grizofulvin. Oh. And scientists
discovered that if they made the drug crystals
super tiny, like ultramicrocrystalline is what
they call it. Wow. the absorption increased by
one and a half times. Wow, that's a big difference.
I know, right? That's huge! So that means patients
could take lower doses for the same effect. And
that could potentially mean minimizing those
side effects. Exactly. Wow, so that just shows
how powerful these little tweaks to a formulation
can be. That's wild, I never would have thought
about that. Yeah, it's just the tip of the iceberg,
though. Oh no. Remember, our bodies are amazingly
efficient at getting rid of things they don't
recognize. They are, they are. So that's where
this concept of ADME comes in. Okay, ADME, what
is that? It stands for absorption, distribution,
metabolism, and excretion. Okay, so it's like
the four horsemen of drugs in your body. Yeah,
exactly. So these four processes, they determine
the fate of any drug that enters your body. Okay,
let's break this down a little bit because...
ADME, it sounds like a pretty important concept.
It is. So absorption, that's like the first step,
right? Yeah. Yeah. Imagine a drug molecule as
a tiny traveler, right? OK. And it's on this
mission. to reach a specific destination in your
body. Absorption is like getting through customs.
How easily the drug gets from its point of entry,
whether that's your stomach or a muscle, into
your bloodstream. Oh, so a pill has to go through
customs at the digestive border. Exactly. Whereas
an injection gets a fast pass right into the
country. Exactly. I like that. OK, so we're through
customs. Now what? Now we're talking distribution.
This is all about how the drug navigates the
transportation system within your body. So your
blood vessels, your tissues, your organs. Making
sure the drug doesn't take a wrong turn. Exactly.
And then comes metabolism. This is where things
get even more interesting. Your body, particularly
your liver, it's like this super efficient processing
plant. OK. So it sees the drug as a foreign substance
and starts breaking it down into these smaller
inactive pieces. So it's like our body's trying
to detoxify. Exactly. OK. So those smaller pieces
are called metabolites. And that brings us to...
to excretion, that final stage, which is all
about removing the drug, or really it's metabolites,
from your body, mainly through your kidneys and
urine. So ADME, is it really like a complex obstacle
course for these drugs? Yes. Scientists are trying
to design formulations to help the drug navigate
the course successfully. You got it. That's a
great way to put it. And that's where the ingenuity
of the formulation scientists really comes in.
They're like the coaches. Yes. They're using
their understanding of ADME to enhance a drug's
chances of reaching its target and actually producing
the desired effect. Wow. So it's really like
a whole team effort. It is. And one way they
do that is by manipulating something pretty simple
as particle size. Particle size. OK. How does
the size of a of the shrug particle matter. Well,
think about it like this. If you're trying to
dissolve a sugar cube in water, it's going to
dissolve a lot slower than a spoonful of granulated
sugar. Yeah, for sure. Right. And that's because
the smaller particles, they have a much greater
surface area exposed to the water. So it dissolves
quicker. Exactly. So smaller drug particles dissolve
faster, meaning they can get absorbed into the
bloodstream more quickly. OK, that makes sense.
And a classic example of this is the heart medication
digoxin. Digoxin, OK. Its absorption can vary
a lot, depending on how finely it's milled. So
if the particles are too big, it might not get
absorbed properly. Exactly. You wouldn't get
the full effect of the drug. Wow. But particle
size, that's just one thing, right? Just one
piece of the puzzle, yeah. So what else are these
scientists doing? They've got a whole arsenal
of tricks. They're adding other ingredients called
excipients. These can do things like enhance
solubility, protect the drug from degradation,
or even control its release over time. It's like
a supporting cast for the drug. Exactly. Working
behind the scenes to make sure that drug delivers
a star performance. I like that. OK, so what
are some examples of these excipients? What do
they do? Well, some of them, they act as buffers
to help control the pH. The pH. Of the drug formulation.
And this is really important for drugs that are
taken orally. OK. Because they need to withstand
that acidic environment of the stomach. Right.
You don't want it to break down before it's even
had a chance to work. Exactly. And then some
other recipients can act as coatings. Coatings,
OK. That protect the drug from moisture or light,
things like that. OK. And some can even be designed
to control the rate at which the drug is released.
Oh, interesting. Yeah. So you can have extended
release formulations. That's cool. so much strategy
goes into this. Here it is. It's not just about
the active ingredient itself, it's all the other
players on the team. Right, and that's where
things get really interesting because the science
of formulation, it can actually be used to improve
existing drugs. To improve existing drugs. Yeah,
for example, scientists might tweak the formulation
of a drug to enhance its absorption. Okay. Or
maybe reduce side effects. So they're like, giving
it a makeover. Yeah, exactly. So it could perform
better. Yeah, and those formulation innovations
can actually be patented. Oh, wow. You know,
which drives progress in medicine and provides
patients with better treatment options. Okay,
well, this brings up something I've always wondered
about. That's it. Generic drugs. How can we be
sure that a generic drug works just as well as
the brand name version? That is a great question,
and that's where bioequivalence studies come
in. bioequivalent studies, okay? Yeah, they're
designed to demonstrate that a generic drug performs
similarly to the brand name drug. Okay. In terms
of its absorption, distribution, metabolism,
and excretion. Oh, so that whole ADME obstacle
course. Exactly, that whole obstacle course.
So it's not just about having the same active
ingredient. No. It's about making sure it behaves
the same way in the body. Exactly, you got it.
As the original drug. Yeah, because even slight
differences in inactive ingredients or the way
it's manufactured, that can impact the drug's
performance. So these bioequivalent studies,
they rigorously compare the generic to the brand
name to make sure they are essentially interchangeable.
OK, that's reassuring. That means patients can
have access to affordable medications without
having to compromise on quality. Right, exactly.
Or effectiveness. It really highlights how critical
it is to understand formulation and those ADME
processes. Now, speaking of ADME, you mentioned
something earlier. Oh, yeah. Called the BCS.
Yeah, the BCS. Yes. What was that again? That's
the biopharmaceutics classification system. Oh,
OK. And it's basically a way scientists categorize
drugs based on their solubility, solubility,
how well they dissolve, and permeability. Permeability,
OK. How easily they cross those biological barriers,
like cell membranes and things like that. So
are there different classes of drugs based on
these properties? There are, yeah. But the most
important thing to remember is the difference
between highly soluble, highly permeable and
those that are not so good at one or both. Okay,
so tell me about the, I guess the superstars.
The superstars. The ones that are both soluble
and permeable. Yeah, those are like the ideal
drugs, the ones that dissolve easily and have
no problem crossing those barriers. Okay. So
in the BCS, we call those class one drugs. Class
one drugs. They're the superstars of drug absorption.
Okay, so for those drugs, it's a breeze to get
into the bloodstream. You could say that, yeah.
And this is where you said the BCS is relevant
to generic drugs. Yeah, so remember those bioequivalent
studies we talked about? Well, for these class
one drugs, scientists can often use a simpler
test called a dissolution test. Instead of doing
the whole study with people. Right, so instead
of testing it in humans, they can just see how
well it dissolves in a lab setting. And the FDA,
they have specific guidelines for this. If the
generic drug dissolves at the same rate and to
the same extent as the brand name drug, it's
considered bio equivalent. Oh, wow. And this
is a huge win for getting affordable generics
to market faster. That's amazing. I never realized
how these properties of a drug could have such
a big impact on generic medications. Yeah, it's
a really interesting interplay of science and
regulation. It's really a testament to how much
thought and effort goes into making sure that
all these medications, whether they're brand
name or generic, are safe and effective for patients.
This whole deep dive is making me think about
how our bodies aren't just passive vessels. They're
dynamic systems that are always changing. and
responding to different things. So wouldn't that
affect how a drug is absorbed and distributed?
That's a great point. You're absolutely right.
Physiological factors or what's going on inside
your body play a huge role in drug absorption.
So the same drug might behave differently in
different people. Exactly. Things like gastric
emptying rate. Gastric emptying rate. Okay. So
how quickly your stomach empties. Intestinal
transit time. even blood flow to the digestive
tract, all those things can influence how a drug
is absorbed. It's like the drug is navigating
a constantly changing landscape. Yeah. Inside
our bodies. Yeah. And that landscape can look
different for everybody. And what about food?
Oh, yeah, food. That can be a major factor, too.
Yeah, because I've definitely had the experience
where, like, I need to take some medications
on an empty stomach. Right. And some with food.
Why is that? Yeah, it all comes down to how those
food components interact with the drug's absorption
process. OK. Sometimes food can enhance absorption,
but in other cases, it can interfere with it.
OK. Like what? Give me an example. Well, let's
talk about grapefruit juice. Grapefruit juice.
OK. It's notorious for interacting with certain
medications. Yeah, I've heard that. So it contains
compounds that can inhibit these enzymes in the
gut that are responsible for drug metabolism.
So it's not just a refreshing drink? No. It's
like a disruptor it can be of drug metabolism
yeah so if the drug isn't metabolized as efficiently
you can end up with higher drug levels in your
bloodstream so it's like amplifying the effect
exactly so that's why it's so important to understand
food drug interactions right yeah Your health
care providers need to be aware of these things
so they can advise their patients. It seems like
all of this points to how individualized medicine
is becoming. Yes. It's not a one size fits all
approach anymore. It's not. You're absolutely
right. We're moving towards personalized medicine
where treatments are tailored to your unique
genetic makeup, your lifestyle, even your dietary
habits. So factors like, you know, how quickly
our stomachs empty or how well we metabolize
certain drugs could influence the medications
and dosages were prescribed. Absolutely. And
as our understanding of all these individualized
factors grows, we're going to see more targeted
and effective drug therapies in the future. Wow.
I'm really seeing the bigger picture here. Yeah.
It's not just about the drug itself. It's about
that whole journey through our body. Yeah. And
how so many different factors can influence that.
It's pretty amazing. It is. It is. How much science
goes into something as seemingly as simple as
taking a pill or getting an injection. Well,
this deep dive has been eye -opening for me.
Glad to hear it. Yeah, it really makes you think
twice of those little pills we take, right? It
does. And it gets even more complicated when
we start talking about these larger molecule
drugs, like protein -based therapies, things
like monoclonal antibodies. Right. Those are
becoming pretty important these days. They are.
They used to treat a lot of different diseases.
They are. delivering these big complex molecules,
it's a whole different ballgame. It's like, you
know, imagine trying to ship a really fragile
antique across the country. OK, I'm listening.
You got to pack it really carefully. That's kind
of what it's like with these large molecule drugs.
They need special care and handling. Because
they're so much bigger than those small molecule
drugs we were talking about earlier. Exactly.
They can be. They can break down easily. They're
degraded by enzymes in the body, and they have
a harder time getting through those cell barriers.
It's like trying to fit a square pig in a round
hole. Yeah, kind of. It's just not going to work
without some creative solutions. So what are
scientists doing? Well, that's where these innovative
delivery systems come in, like nanoparticles
and microspheres. Nanoparticles and microspheres.
Those sound pretty fancy. They are. So think
of them as these tiny little protective capsules.
OK. They they basically encapsulate the drug
and shield it. So it doesn't break down. Exactly.
They keep it safe from being broken down before
it reaches its target. So going back to your
antique analogy, it's like giving it a custom
designed crate. Yes. And like a team of expert
movers to make sure it gets there in one piece.
Exactly. And these delivery systems, they're
already being used for a lot of different things.
Like what? like cancer treatments, vaccines.
It's really changing how we give these powerful
medications. So it's getting really specific
and customized. It is. It's all about finding
the perfect way to get those molecules where
they need to go. And I bet technology is playing
a huge role in all of this. It is. Technology
is really transforming the field of drug delivery.
Yeah. We're seeing so many advancements in 3D
printing, microneedles. It's incredible. Like
3D printing for medicine? Yeah. So imagine your
doctor prescribes you a medication, but instead
of going to the pharmacy, Mm -hmm. They just
point it right there in the office. No way. Tailored
just for you. So we could have personalized doses?
Exactly. And then there are micro needles. Why,
crew needles? Okay. These are tiny, painless
needles that deliver drugs through the skin.
So no more painful injections. It's definitely
a lot less intimidating, which could help people
take their meds as prescribed. That's huge, especially
for people who are afraid of needles. Yeah, it
could really make a difference. It's amazing
how far we've come with drug delivery. It is.
From changing particle size to these high -tech
delivery systems, it's really incredible. It
really shows you the ingenuity and dedication
of these scientists who are working to improve
people's health. So next time we take any kind
of medicine, we should remember all the amazing
science that went into it. Absolutely. It's not
as simple as it seems. Well, this deep dive has
definitely given me a whole new perspective on
the world of drug formulation and delivery. Me
too. It's a fascinating field. And who knows
what the future holds. Yeah, there's so much
more to discover. Well, thanks for joining me
on this deep dive. It was my pleasure. And to
our listeners, stay curious.