Basic introduction to Biopharmaceutics and Pharmacokinetics

1. Biopharmaceutics &
Pharmacokinetics
Presented By: Mrs. Mehetre Gitanjali S.
Designation: Assistant Professor
Department: Pharmaceutics

2. Absorption of Drugs

3. Drug
• Thus, absorption is an important
prerequisite step
 A drug is injected
intravascularly (iv or im)
directly enters into systemic
circulation.
 Majority of drugs are
administered extravascularly
(generally orally).
 Such drugs can exert the
pharmacological action only
when they come into systemic
circulation from their site of
administration .

4. Definition ofAbsorption
• The process of movement of unchanged drug from the site of administration
to systemic circulation.
• The effectiveness of a drug can only be assessed by its concentration at the
site of action.
• It is difficult to measure the drug concentration at such site.
• Instead, the concentration can be measured more correctly in plasma.
• As there always a correlation between the plasma concentration of a drug &
therapeutic response.

5. Cell Membrane: Structure &Physiology

6. Cell Membrane:
 Cell membrane separates living cell from nonliving
surroundings
 Thin barrier = 8nm thick
 Controls traffic in & out of the cell
• selectively permeable
• allows some substances to cross more easily than others
hydrophobic vs hydrophilic
 Made of phospholipids, proteins & other macromolecules

7.  Proteins determine membrane’s specific functions
– cell membrane & organelle membranes each have
unique collections of proteins
– Membrane proteins:
- peripheral proteins
• loosely bound to surface of membrane
• cell surface identity marker (antigens)
- integral proteins
• penetrate lipid bilayer, usually across whole
membrane
• transmembrane protein transport proteins
– channels, permeases (pumps)

8. Mechanisms Of DrugAbsorption
A) Transcelluar transport
 Passive transport processes
• Passive diffusion
• Pore transport
• Ion-pair transport
• Facilited diffusion
 Active transport processes
 Primary active transport
 Secondary active transport
• Symport
• Antiport
B) Paracelluar transport
 Persorption
 Permeation through tight junctions of cells
C) Vesicular transport
 Pinocytosis
 Phagocytosis

9. 1. PassiveDiffusion
 Diffusion
 Movement from high to low
concentration
• Major process for absorption of
more than 90% of drugs
• Non ionic diffusion
• Driving force – concentration or
electrochemical gradient
• Difference in the drug
concentration on either side of
the membrane
• Drug movement is a result of
kinetic energy of molecules

10. Mathematically (Fick’s First lawof diffusion)
.................I
dQ/dt = rate of drug diffusion (amount/time)
D = diffusion coefficient of the drug
A= surface area of the absorbing membrane for drug diffusion
Km/w = partition coefficient of drug between the lipoidal membrane &
the aqueous GI fluids
(CGIT – C) = difference in the concentration of drug in the GI fluids &
the plasma (Concentration Gradient)
h = thickness of the membrane

11. Characteristics of Passivediffusion
Energy independent & non-saturable
Greater the area & lesser the thickness of the membrane, faster
the diffusion
The process rapid over for short distances
Concentration equal on both the sides of the membrane -
equilibrium is attained
Greater the Partition Coefficient of the drug faster the
absorption
Molecular weight between 100-400 Daltons are effectively
absorbed

12. But this is not the case……
The passively absorbed drug enters blood, rapidly swept away
& distributed into a larger volume of body fluids
Hence,
The concentration of drug at absorption site CGIT is maintained
greater than the concentration in the plasma. Such a condition is
called as sink condition for drug absorption.

13. Under usual absorption conditions,
D, A, Km/w & h are constants, the term DAKm/w /h can be replaced by
a combined constant P called as permeability coefficient
Permeability - ease with which a drugcan permeate or diffuse
through a membrane.
Due to sink conditions, the C is very small in comparison to CGIT.

14. 2. PoreTransport
• It is also called as convective transport, bulk flow or filtration.
• Mechanism – through the protein channel present in the cell
membrane.
• Drug permeation through pore transport – renal excretion, removal
of drug from CSF & entry of drug into the liver

15. The driving force – hydrostatic or osmotic pressure differences across
the membrane. Thus, bulk flow of water along with the small solid
molecules through aqueous channels. Water flux that promotes such a
transport is called as solvent drag
The process is important in the absorption of low molecular weight
(<100D), low molecular size (smaller than the diameter of the pore)
& generally water soluble drugs through narrow, aqueous filled
channels or pores e.g. urea, water & sugars.
Chain like or linear compounds (upto 400D) absorbed by filtration

16. 3. Ion-pairTransport
Responsible for absorption of compounds which ionizes at all
pH values. e.g. quaternary ammonium, sulphonic acids
Ionized moieties forms neutral complexes with endogenous ions
which have both the required lipophilicity & aqueous solubility
for passive diffusion.
E.g. Propranolol, a basic drug that forms an ion pair with oleic
acid & is absorbed by this mechanism

17. 4. Carrier MediatedTransport
• Involves a carrier which
reversibly binds to the
solute molecules and forms
a solute-carrier complex
• This molecule transverse
across the membrane to the
other side and dissociates,
yielding the solute molecule
• The carrier then returns to
the original site to accept a
new molecule.
• There are two type of carrier mediated
transport system
1) Facilitated diffusion
2) Active transport

18. 5. FacilitatedDiffusion
• Facilitated diffusion is a
form of carrier transport
that does not require the
expenditure of cellular
energy.
• Carriers are numerous in
number & are found
dissolved in cell membrane.
• The driving force is
concentration gradient,
particles move from a region
of high conc to low conc.

19. ActiveTransport Processes
• Requires energy, which is
provided by hydrolysis of
ATP for transportation.
• More commonly, metabolic
energy is provided by the
active transport of Na+, or is
dependent on the
electrochemical gradient
produced by the sodium
pump, Na+/K+ ATPase
(secondary active transport).

20.  PrimaryActiveTransport
• Direct ATPrequirement
• The process transfers only one ion or molecule & only in
one direction. Hence, called as UNIPORT
• E.g. absorption of glucose
• ABC (ATP binding Cassette) transporters

21.  Secondary active transport
• No direct requirement ofATP
• The energy required in transporting an ion aids transport of
another ion or molecule (co-transport or coupled transport)
either in the same direction or opposite direction.
• 2 types:
• Symport (co-transport)
• Antiport (counter transport)

22. Symport
Antiport
A
TP A
TP
Antiport And Symport

23. Endocytosis
• It is a process in which cell
absorbs molecules by engulfing
them.
• Also termed as vesicular
transport.
• It occurs by 3
mechanisms:
 Phagocytosis
 Pinocytosis
 Transcytosis

24. Phagocytosis

25. Transcytosis
• It is the process through which
various macromolecules are
transferred across the cell
membrane.
• They are captured in vesicles,
on one side of the cell and the
endocytic vesicle is transferred
from one extracellular
compartment to another.
• Generally used for the
transfer of IgA and insulin.

26. Pinocytosis
• It is a form of endocytosis in which
small particles are brought to the
cell, forming an invagination.
• These small particles are suspended
in small vesicles.
• It requires energy in the form
ofATP.
• It works as phagocytosis, the only
difference being, it is non specific in
the substances it transports.
• This process is important in the
absorption of oil soluble vitamins
& in the uptake of nutrients