Biopharmaceutics
‫لجان الدفعات – كلية الصيدلة‬
Dr. Rana Abu-AlDahab
2010 ‫دفعة‬
Lecture-2- Isra’a Najdi
lecture 2:
Physiologic Factors Related to Drug Absorption
The systemic absorption of a drug is dependent on
(1) the physicochemical properties of the drug,
(2) the nature of the drug product
(3) the anatomy and physiology of the drug absorption site
First we are going to take about number (3) the anatomy and physiology of the drug absorption site
When a drug is administered by an extravascular route of administration (eg, oral, topical, intranasal,
inhalation, rectal), then the drug must first be absorbed into the systemic circulation ( means cross the
membrane ) and then diffuse or be transported to the site of action before eliciting biological and
therapeutic activity.
Bioavailability of the drug at the absorption site depend on two parameters :
1) Physicochemical proprieties of the drug such as lipid soluble, water soluble ,is it able to link with a
carrier or not
2) Nature of Cell Membranes: Membranes are major structures of cells, which consider as important
value for drug delivery
Properties' of the cell membrane is :
 Important barrier of drug delivery
 major structures of cells
 enclose cellular content and organelles so prevent the organelles from escaping from inside the
cell
 semipermeable partitions that act as selective barriers to the passage of molecules
 Cell membranes are generally thin, approximately 70 to 100 Ã… in thickness
 Composed primarily of phospholipids in the form of a bilayer interdispersed with carbohydrates
and protein groups
Review :
Phospholipids : give the membrane structure ( mean the frame work of the membrane consist of
phospholipid bilayer ) there is phosohotadil colin \ syrine \ inositel its mostly unsaturated phospholipids
Carbohydrates are always on the exterior surface
Glycoprotein : protein link with sugar
Protein : act as a carrier, receptor, linker and channels
There are several theories of the cell membrane structure :
1. The lipid bilayer or unit membrane theory :
They knew there's a major barrier and they considers the plasma membrane to be composed of two layers of
phospholipid between two surface layers of proteins ( so notice here that protein could be either under the
surface or outer the surface ) , with the hydrophilic "head" groups of the phospholipids facing the protein
layers and the hydrophobic "tail" groups of the phospholipids aligned in the interior. The lipid bilayer theory
explains the observation that lipid-soluble drugs tend to penetrate cell membranes more easily than polar
molecules. However, the bilayer cell membrane structure does not account for the diffusion of water, smallmolecular-weight
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Biopharmaceutics
Dr. Rana Abu-AlDahab
Lecture-2- Isra’a Najdi
2. The fluid mosaic model:
explains the transcellular diffusion of polar molecules. According to this
model, the cell membrane consists of globular proteins embedded in a dynamic fluid, lipid bilayer matrix .
These proteins provide a pathway for the selective transfer of certain polar molecules and charged ions
through the lipid barrier.
Here fluid mean structure is not rigid (not one unit) so it’s a flexible membrane .In this theory we could
explain the way that drug transport
3. Lipid membrane structure in the relation to drug research :
They said when they try to transfer a drug to cross the membrane they notice they view the membrane in
different manner from the first and second theory. which I mean that when they put a molecular which is
really hydrophobic its transfer is less than what the theory expected and that apply to hydrophilic
molecule too so they try to go back again and study the structure to explain that.
So they view the cell membrane composed of 4 sub layers : (stratified layer)
 Layer 1: perturbed water layer : when we put the molecule on the surface of the cell membrane it'll
face layer1 ( perturbed water layer) this layer its chemically heterogeneous water layer but its
different from the free water
H2O is a unique molecular bound by H bound its able to move but there's something called bound
water we would find it in the protein. The environment of the cell is aquas and the protein sometime is
contain pockets which make hydrogen bound with water outside and hydrophobic inside it
To make the pocket stable water molecule make H bound with this part of protein but these water
called bound water (it’s H2O but its not move or replace it with another one ) because if its move it
would lead to protein change so these water we call it bound water its have different characteristic
properties from free water its different in the freezing we know that free water freeze at zero C but
bound water freeze at -20,-40 C
So extra cellular fluid all its water so when we come close to the layer which has the hydrophilic head
we would found the perturbed water layer
Summary : this layer is chemically heterogeneousness with polarization properties that are different
from ordinary water reflected by dielectric constant and freezing

Layer 2: hydrophilic/ hydrophobic layer including bound water lipid polar head groups and parts of
the upper acyl chains
This layer is not hydrophilic or hydrophobic because its contain the above .
 Layer 3:conformationally ordered acyl chain segments its hydrophobic layer
 Layer 4:conformationally disordered acyl chain segments its hydrophobic layer
Why the layer 4 is disorder ?
Because in this layer we ‘ll be In the fatty acid section and we know that not all the fatty acid has the
same length some of them 16 or 18
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Biopharmaceutics
Dr. Rana Abu-AlDahab
Lecture-2- Isra’a Najdi
So now when the molecule want to enter the cell membrane it has to go through all these layer in this
order (1-2-3-4then4-3-2-1)
[Picture]
membrane asymmetry
which cause the asymmetry of the membrane is due to : phospholipids and protein
the asymmetry is begin from the starting of arrangement of the membrane ( during the biogenesis ) we
need to know if the symmetry happened is maintain this is because of the limited movement
and now the movement of lipids in the bilayer is either :
1) Flip flop this movement isn’t common because it is not thermodynamic favorable
2) But they can rotate around their axis
3) Or they can has lateral movement
The effect of sterol on membrane fluidity :
Sterol is inserted inside the membrane in the both side but mostly on the hydrophilic part its function is
to maintains rigidity and improve the rigidity .If we increase the temp the fluidity is goanna to increase
too and vice versa
So to limit the sol state (it's an increase in fluidity at high temp) or gel state (it’s a decrease the fluidity
more rigid at low temp) the cholesterol is presence
Cholesterol has paradoxes effect on the membrane : what I mean is
When the temp is high the membrane become more fluid but the presence of cholesterol limit the
fluidity and vice versa
Membrane protein :
Every protein has hydrophilic and hydrophobic part
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Biopharmaceutics
Dr. Rana Abu-AlDahab
Lecture-2- Isra’a Najdi
We need to know that lipid anchored membrane protein is more rigid bound on the surface by
covalent bound with lipid, but the peripheral protein has electrostatic interaction or anchored by
covalent bound.
Lipid protein interaction :
There sometime interaction to maintain structure this happened mostly by hydrophobic and
hydrophilic part matching of phospholipids with protein this is would lead to lipid sorting and lipid
selectivity and this matching happened during the biogenesis
Transport of drugs across cell membranes
Simple or passive diffusion
Passive diffusion is the process by which molecules spontaneously diffuse from a region of higher
concentration to a region of lower concentration. This process is passive because no external energy is
expended. The rate of transfer is called flux, and is represented by a vector to show its direction in space.
Passive diffusion is the major absorption process for most drugs The driving force for passive diffusion is
the conc. Gradient
Fick's law of diffusion
where dQ/dt = rate of diffusion, D = diffusion coefficient, K = lipid water partition coefficient of drug in the
biologic membrane that controls drug permeation, A = surface area of membrane; h = membrane
thickness, and C GI and C p = difference between the concentrations of drug in the gastrointestinal tract
and in the plasma.
We need to know if the rout of administration is different then the rate will different too for example if we
have 100 molecule of the drug and w apply it on the lung or nasal the absorption rate it different because
the membrane thickness and the surface area is different the rate will be higher at the lung because it has
higher surface area
Note : you need to refer to the sheet to get a complete picture
[THE END]
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