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2. Core Areas of Pharmacy
1. Drug Design
Involves designing and synthesizing compounds to find a
specific chemical substances that will cure, manage or
prevent diseases: Cancer, AIDS, Ebola
2. Drug Formulation
Mix various chemical compounds with the drug to create
Tablet ,Suspension, Emulsion, Injection.
(These chemicals should not react with drug)
3. Drug Dispensing
Give the right drug to the right patient in right dose and
duration with sufficient counseling
(Biopharmaceutics has application on all three above)
4. Others (manufacturing,marketing and regulatory issues)

3. Drug?
• Drug is a specific organic compound which has
therapeutic effect (forget inorganic drugs like
MgOH from now on)
Metformin
Diabetis
Imatinib
Cancer
Lidocaine
Local Anesthetic
Paracetamol
Anti-inflamatory
Nelfinavir
AIDS
Omeprazole
Ulcer

4. Paracetamol
Anti-inflamatory
•How to consume?
•How much to consume?
•What happens if instead of 3 tablets, we take 6 or 9 tablets of
paracetamol on hopes of better or quicker recovery?
•How about we share a single tablet between two person?
•How much is too much or too less?
Understanding “Bio” in biophamaceutics

5. First of all….Pharmaceutics
• Pharmaceutics is science dealing with drug
formulation
• Drug formulation means process of mixing
drug with other chemicals to prepare a
physical form which facilitates convenient
dosing(intake) for patients
• That physical forms are Tablets, suspension,
emulsion, syrup or solutions. This is also called
oral dosing

6. Various dosage form

7. Basic understanding of drug formulation
Formula of Paracetamol tablets
•Drug is never given in pure form but as an intended mixture with other chemicals to
help attain a physical form
•These other chemicals are called excipient
•Excipients don’t react with each other or with the drug

8. There are many choices for various excipient classes
from which many formulation of same drug in same
strength can be made
Excipient
Fillers/Diluent
(Allows making a
sizable tab if drug
content is very less)
Lactose,lactose anhydrous, lactose spray dried, directly
compressible starch,hydrolyzed starch, MCC, other cellulose
derivatives, dibasic calcium phosphate dihydrate, mannitol,
sorbitol, sucrose, calcium sulfate dehydrate, dextrose.
Binders
(allow drug power to
be compressed into a
solid tablet)
cellulose, methyl cellulose, polyvinyl pyrrolidine, PEG, gelatin,
PVP, HPMC, PEG, sucrose, starch
Disintegrating agent
(breaks hard solid tab
to free the power
drug from tablet)
starch derivatives, clay, cellulose, alginates, PVP, cross linked Na
CMCVeegum HV and Betonite PVP, CMC ,crospovidone, Sodium
bicarbonate
Lubricant Stearic acid, stearic acid salt, stearic acid derivatives, talc, PEG,
surfactants,waxes, Calcium stearate and magnesium stearate
poly ethylene glycol
Glidant talc, colloidal silicone dioxide, corn starch

9. First thing to do…..
• Understand that ALL drugs must be present in blood/plasma
to show effect (excluding topically (skin, eye, ear) applied
creams, gels etc)
• Depending on drug concentration in plasma either of three
results: no effect, therapeutic effect, side/toxic effect of drug
• This information is the first thing obtained during drug Human trials.
Thus we already know how much drug must be present in blood for
therapeutic effect to occur
• When we take a single dose, our interest is to provide just enough
drug to keep the drug conc within the therapeutic region
No effect Therapeutic effect Toxic effect
Effect of Increasing blood concentration on blood

10. Secondly, think about the time course of a drug
The drug conc in plasma varies continuously after we take a single dose
We cannot keep on maintaining drug conc in the therapeutic region by
only a single dose. Thus we need to give another dose
But what factors are making drug concentration to decrease and
How to know when to give another dose?????

11. • To make sense of above graph following
phenomenon have to be considered
– Absorption – drug enters blood circulation by
process of diffusion
– Metabolism – drug structure is enzymatically
altered
– Distribution – drug is distributed from blood to
fat, muscle, organs
– Elimination – Drug is thrown out from body
• Study of these 4 parameters is called
pharmacokinetics

12. Think about this!!!
• Now that we know what is the range of conc for a
drug to be in body, we could simply calculate the
amount of drug in a single dosage form
• Eg if paracetamol is to be maintainted at 50mg/Lt
plasma volume…considering an avg of 2.7 lt of
plasma in body, we could say that a single PCM
tablet needs to have 50X2.7= 135 mg
• However this type of assuption is wrong.
Determining amount of drug in a single dose is
not that simple because the body does not
behave like a vessel containing 2.7 lt of solvent.
• Body presents a dynamic environment to a drug
where the conc of drug is continuously changing

13. Understanding Absorption
Absorption occurs when drug dissolved in intestine diffuses through
the epithelium and into the capillaries (which is hepatic portal vein
which takes the drug to the liver)
(Notice the blood capillaries
into where drug diffuses)

14. Diffusion
• The spontaneous movement of solutes from high to low conc until
equilibrium is diffusion. It occurs in solution only.
• For purposes to study drug diffusion in body we consider diffusion
in the scenario where there are two compartments, left being
stomach and right being blood, and both being separated by the
lipophillic cell membrane epithelium
Let this compartment
represent drug dissolved
in stomach fluid
Let it represent
drug dissolved
in capillary
blood/plasma
Epithelium cell
membrane

15. Two opposing characteristic for good
absorption
• Diffusion through the epithelium requires crossing the
cell membrane of the epithelium which is lipophilic
barrier. This requires drug to have such structure
which gives it good lipophillicity.
• But since diffusion occurs only in solution, drug must
dissolve into the stomach fluid first. This requires drug
to have such structure which gives it good
hydrophillicity.
• (remember hydrophillicity and lipophillicity depend
are physiochemical properties that solely depend on
drug structure)
But drug is in form of a tablet. So how does a tablet dissolve?

16. Disintegrating agent!
• A tablet is a relatively hard substance. We
swallow it whole without chewing. That sounds
problematic (coz we always chew our food to
make digestion easy) but there are chemicals
added into the tablets called disintegrating agent
(in above Crosspovidone and Sod bicarbonate)
which swells up when in contact with water and
this causes tablet to break apart spontaneously.
• (Show tablet disintegration in a glass of water)

17. Show tablet disintregation in water
• Put various brands of 500mg paracetamol
tablets in water and observe that
– Tablet spontaneously breaks apart due to the
disintegrating agent soaks up water and expands,
thus causing tablet to break
– various brands disintegrate at different time and
to different degree
• This diff is due to diff in formulation which be
as we saw there are multiple choice for
particular excipients

18. Understanding Absorption is
important because….
• Many drugs have failed to be orally active
because they were too soluble and thus cant
permeate through the cell membrane
• Or they were too lipophillic and can’t dissolve in
stomach fluid (remember: diffusion requires drug
to dissolve in aqueous stomach fluid)
• Point is…..just cause we consume a drug doesn’t
mean there is guarantee of being absorbed
(however, for such problematic drugs,
formulation enhancement cab be done which we
will study later in course)

19. Metabolism
We saw that drug in a tablet
disintregates into smaller particles and
then dissolves to the extent depending on
its solubility which then diffusion through the epithelium into
the capillary. But it hasn’t quiet reached systemic circulation
• This capillary is names hepatic portal vein which goes to
the liver and then to the heart. As it flows through the liver
the drug are acted upon by special enzymes (other than
those involved in biological reactions) dedicated to
destroying endogenous substances.
• This is metabolism and it happens primarily in the liver
• The first time this happens is called 1st pass metabolism
and only applies to oral drugs

20. Metabolism of paracetamol
• Notice that paracetamol structure
changes- that is metabolism
• These metabolized products generally
lack any therapeutic use
• And are more water soluble for easy
removal by urine
Although it might seem that metabolism is a bad thing in that it destroys our drug,
We can overcome it by simply consuming more dose in compensation. Orally we can take
about 1gm dose. Any more compensation and the tablet would be too big to swallow
Also later on we will incredibly exploit this process in our favor in prodrugs

21. • Body responds to all endogenous substances, poison or
drugs, as if it were a threat and wants to detoxify them
and clear them out of body
• The enzymes alter the drug structure so that the
product is more water soluble.
• The increased water solubility is important since the
main path to clear the drug is through urine. Thus the
more soluble in urine, more quickly drug can be
cleared.
• Metabolism is another reason that any oral dose does
not fully reach the plasma as they get changed into a
diff compound along the way, even if absorption was
very good
• If liver get diseased causing reduced metabolism of
drugs then more drug are able to enter into the body.
This over exposure can cause toxic conc to build up!

22. Elimination
• Elimination can be seen as a two stage process
– 1st drug is metabolized by the liver into more water soluble form
– 2nd as blood flows through kidney, the now more water soluble form
is excreted (filtered) into the urine (an aqueous fluid)
• The more quickly elimination occurs, more quickly we need
another dose and vice versa
• Understand that without metabolism, excretion can difficult
cause drugs are mostly lipophilic
• So now we know that a drug action can’t be forever cause it
gets either destroyed by liver or excreted by kidney
• If kidney is damaged resulting in less filtration , than drug stays
in body for longer period of time!
• But what about giving drug to patients with both liver and
kidney damage?

23. Metabolism worked together with urinary excretion
Elimination also
occurs through bile
Oxidation and conjugation are two
types of metabolism that we will study later
Polar
Metabolite
go to urine

24. Distribution
Once drug passes through the liver it enter blood
circulation and can go everywhere the blood carries it

25. Distribution
Distribution takes place once drug has entered blood. As the pic
demonstrates of the given 10mg, only 1 mg is seen in the plasma. Thus
drug does not localized in the blood but can distribute itself out of
circulation into tissues, fat and even be bound to plasma protein.
Distribution is a problematic because, it lowers the conc of drug in
plasma and it is conc of drug and not the amount which determine
Once in blood , drug can go
to all places inside body

26. Long acting drug!!!
• An important concept is that distribution follows dynamic
equilibrium.
• Once distributed drug does not keep being trapped in fat,
tissues or plasma protein
• As the free drug in the plasma is metabolized and excreted,
the vacancy in plasma causes the distributed drug to again
come back to plasma
• In this way distributed drugs act like a reservoir which
sustains the conc in the plasma
• This can be exploited to make drugs with high distribution
so that they remain the body for a long period of time
compared to drugs that have low distribution (there is still
no way to avoid metabolism and excretion but this way
drug can act for a longer time period)

27. Conclusion
• We want drug to be within predefined conc range in blood
but we can’t simply treat body as a 5 lt vessel of blood.
• There are barriers for drug to maintain sufficient
concentration in plasma, in that they make sure that not all
the given dose can be reaches plasma (absorption) and
those that do reach plasma have difficult maintaining the
therapeutic concentration as drug is being structurally
altered (metabolism), diluted (distribution), kicked out
from the body (elimination)
• Thus we need to account for all these factors and decide
what should be the dose and frequency for every drug
cause these drugs have variable ADME
• This is the true essence of Biopharmaceutics

28. D
E
A
M

29. • Biopharmaceutics is defines as the study of
factors influencing the rate and amount of drug
that reaches the systemic circulation and the use
of this information to optimize the therapeutic
efficacy of drug products
• Biopharmaceutics concerns making such a
formulation of drug and defining its frequency of
dosing, by consideration of the ADME of a
drug,which ensures that the amount of drug in a
single dose (and repeated doses) achieves (and
then is maintained) in therapeutic drug conc in
plasma

30. • Pharmacokinetics is the study of time course of drug
ADME, and their relationship with it’s therapeutic, toxic
effects of drug
• Eg of Pharmacokinetic manipulation,
Distribution based -Vit k gelatin capsule is dosed at 60000
IU. Normal everyday dose is about 300-500IU. Thus 60 K IU
sounds to much (too much of anything is bad!!!) but won’t
be cause vit k being lipophillic gets stored in fat which is
released slowly in blood thus not only acting like a reservoir
of vit k but also ensuring small conc in blood. It means vit k
can be dosed once weekly but still body gets the needed
amount everyday

31. At last….
• A challenge in BioPham is to come up with a
method to predict time dependent changes in
drug conc
• They have been able to do that by building some
mathematical models (ie equation) that can
predict what would a drug conc be in any time in
body
(Don’t be afraid of the math portion. It’s the theory
that will be harder to comprehend. You probably
solved many tough problems based on equation of
motion; it is similar. There are some equation and u
just need to understand which one to use where)

32. THANK YOU