Clare Strachan: Light provides new opportunities to understand and control tablet design
Making a tablet is like baking, drug developers have to find the perfect recipe to make a safe and effective medicine. Scattered light can help in this task, says a …
Today, I'm going to talk about the way we use
light to understand and optimise medicines.
First, I'd like you to take a
look at what I've in my hands.
I've a tablet in one hand
and a croissant in the other.
They look very different, –
but I'd like you take a moment to think
about what they actually have in common.
They are more similar
than you might imagine.
They both have been
made according to a recipe.
They both include carefully selected ingredients,
with a defined amount of each ingredient.
Not too much, not too little.
The ingredients have been mixed
in a certain way and processed –
to get either this
tablet or the croissant.
So, making a medicine,
in this case a tablet, is like baking.
But let's also think about the differences
between the tablet and the croissant.
What happens if the
croissant recipe is not perfect, –
or we are not so skilled
at following the recipe?
The croissant won't taste so good, –
or it won't have that nice
'melt in your mouth' feeling.
That's not good, but it's not so dangerous.
We can work on improving the
recipe and make it taste better.
Perhaps by trial and error,
until we are happy with the result.
But what happens if the
tablet recipe is not perfect?
Let's think about what
ingredients are in the tablet.
Well, one of the tablet ingredients,
of course, is the drug.
That's the very reason
we are taking the tablet.
We take the tablet, because we want
these drug molecules to treat a headache, –
or high blood pressure,
or cancer, for example.
But there are other important
ingredients in the tablet, too.
Each has its own function.
Some ingredients help the tablet
to be formed in the first place.
Others protect the drug from
degrading during storage in pharmacy, –
or in your own home, –
while other ingredients control what
happens to the tablet after we swallow it.
So, what does happen to the tablet,
once we swallow it?
it travels to our stomach and intestine.
Then, the liquids there allow the
drug molecules to leave the tablet, –
and the drug molecules
pass into our blood –
before reaching the place
in our body where we need it.
Our head, for example, to treat a headache.
Or a tumour to treat cancer.
What is crucially important here
is the amount of drug in our blood –
at any one time.
There should not be too much
or too little drug in the blood.
Too little: a headache won't go away.
Too much: we get unwanted side
effects. Some of them can be dangerous.
what affects how much drug is in the blood?
It partly depends on what happens to
the tablet in our stomach after swallowing.
The tablet might break apart and
release the drug molecules all at once.
Then, the drug quickly reaches
the blood in high amounts.
We want this, if the drug should act quickly
to relieve our headache, for example.
Or, the tablet might stay whole and release
the drug molecules slowly, over the whole day.
We would want this slow drug release if,
for example, –
we want to keep our blood
pressure constant all day.
Not too high and not too low.
So, how do we control
what happens to the tablet?
Whether it breaks apart, or not?
And how fast the drug molecules
are released from the tablet, –
even if it does not break apart?
This is where that recipe, the tablet
recipe, or tablet design, is so crucial.
If we don't get the recipe right, we might not
get the right drug release from the tablet, –
and it won't reach the blood
at the precise rate we need.
The medicine might not work at all,
or not work how we intended.
In other words, the consequences
of the tablet recipe not being perfect –
can be deadly serious.
This is not just the case
of a bad-tasting croissant.
So, what do we need to ensure –
that the drug molecules are released
from the tablet in the way we need, –
so that the medicine is safe and effective?
we need a perfectly designed tablet.
We need the right ingredients
in addition to the drug.
We need them in the right amounts, –
and they need to be combined in a very precise
way to get the correct tablet structure.
We need to know and control exactly where
all of the ingredients in the tablet are, –
and that, until recently, has been difficult
at best, and in many cases impossible.
This is why I want to talk about the
power of light with modern medicines today.
I'm going to talk about how our
research group uses light in new ways –
to design safer and
more effective medicines.
If I take this laser pointed
here [scraping sound].
And I shine it on the tablet.
You can see the tablet turning red,
where it hits the tablet.
This is due to the
tablet scattering the light.
But there are other, more subtle interactions
between the light and the tablet, too.
Some of the light is being absorbed
by the tablet and heating it up.
Some of the light is even being scattered in
a way that produces light with new colours.
This is a process known
as 'raman scattering'.
Its name comes from a famous
Indian physicist, sir C.V. Raman, –
who was one of the first to observe
the scattered light with new colours.
When I shone the laser onto the tablet,
you couldn't see these different colours, –
because our own eyes are not sensitive to
detect it, but modern optical sensors can.
So, what exactly determines what
new colours are scattered from the tablet?
Well, it depends what
ingredients we have in the tablet.
This means we can analyse the scattered light
to identify what exactly is in the tablet.
We can use this to check if we have the right
ingredients in the right amounts in the tablet.
Or even to detect counterfeit medicines.
You may have seen this type of detection
being used in a border control programme –
to detect illegal drugs at the airport.
The analysis gets even more powerful,
if we combine the laser with a microscope.
Then, we can detect exactly where
each ingredient is in the tablet –
and how it is interacting with
the other ingredients in the tablet.
And when I say 'exactly where', –
I mean down to a thousandth
of a millimetre or less.
That's about the precision about 70-times
thinner than a strand of your own hair.
Is this level of precision needed?
Do we need to understand the
tablet structure on such level?
A short answer is 'yes'.
Let me illustrate this with two examples.
The first is the surface of the tablet.
You may have noticed
that tablets are often coated.
Coatings can be just used to make
the medicine look or taste nicer, –
but often they have a much
more important function.
They stop the medicine from
breaking apart in the stomach, –
and depending on the
thickness of the coating, –
they control how fast the molecules
are released from the tablet.
Our research group has shown
that a special type of laser microscope –
that detects scattering of
light with different colours, –
that's called a 'coherent raman microscope, –
can be used to image tablet coding distributions
down to a thousandth of a millimetre.
We have shown that differences in the coating
thickness of a few thousandths of a millimetre, –
as detected by this microscope, –
can mean that the drug is released from the
tablet more than five times faster or slower.
That can be the difference –
between a medicine being safe and
effective or ineffective and dangerous.
The second example I would like
to share with you involves crystals.
You may be surprised to learn that tablets
sometimes contain thousands of crystals.
Not diamond crystals,
but drug crystals.
The number and size of these crystals affect –
how the drug is released from the tablet
into the liquid in the stomach or intestine.
Most people think of crystals
as nice and attractive, –
but drug crystals can be bad news.
If there are too many or they are too big, –
the drug maybe released
from the tablet too slowly, –
and not enough drug will reach your blood.
We have used the coherent raman
microscope to detect and image single, –
tiny crystals in tablets, much smaller
than the thickness of a human hair.
Such levels of crystals have been difficult
or impossible to detect in the past.
We have shown that even
a few of these tiny crystals –
can have a dramatic effect on
drug release from the tablets.
That can mean the difference between a medicine
being safe and effective or ineffective.
These are just two examples showing the
power of light to understand and optimise –
the structure or design of medicines.
But I hope that during this presentation, –
I've convinced you about how light is
providing amazing new opportunities –
to precisely understand
and control tablet design.
While our research group is based in the faculty
of pharmacy at the university of Helsinki, –
our research could not be done
without the help of all sorts of experts.
We collaborate with optical scientists,
analytical chemists, –
statisticians and clinicians.
These experts are in Finland, in
Europe and further, as far as New Zealand.
Together, we use light to better
understand and optimise medicine design.
The new levels of understanding make
the medicine safer and more effective, –
and they can prevent very
costly drug development failures.
We don't just look at tablets: we
look at many types of medicine.
inhaled medicines to name a few.
The insights gained are important,
no matter what the medicine is used for, –
be it cancer,
high blood pressure or a simple headache.
So, the next time you take a medicine,
whatever the reason, –
spare a thought for how it was designed.
And perhaps you will remember
that behind the scenes, –
we and other research groups are
employing light in amazing new ways –
to make the medicine you take
even safer and more effective.