Biopharmaceuticals

1. An Assignment on
Mechanism of
Absorption
Submitted by
Roll:-14308
Reg:-1086
Date of Submission:-02/03/21
Submitted to
Mr Mohammed Kamal Hossain
Assistant professor
Department of Pharmacy,
University of Science and Technology
Chittagong (USTC)
Department of Pharmacy
Course Name: Biopharmaceutics-I
Course No:-PHR-305

2. Biopharmaceutics: Branch of pharmaceutics ( pharmaceutical sciences ) dealing
with the study of relationship of physicochemical properties of drugs and drug
products with their pharmacological and therapeutic activities in man and animals.
Biopharmaceutics is the study of the factors influencing the bioavailability of a
drug in man and animals and the use of this information to optimize
pharmacological and therapeutic activity of drug products. Examples of some
factors include:
 Chemical nature of a drug )weak acid or weak base)
 Physicochemical properties of drugs )pKa, particle size and size
distribution, partition coefficient, polymorphism, etc.).
 Inert excipients used in the formulation of a dosage form )e.g. diluents,
binding agents, disintegrating agents, coloring agents, etc.)
 Method of manufacture )dry granulation and/ or wet granulation)
Introduction
Physicochemical
properties of drug
and drug products
Pharmacological
/therapeutic activity
of drug and drug
products
Biopharmaceutics is the
study of relationship
between these two
areas

3. Pharmacokinetics:-refers to the studies of rates of drug absorption, distribution,
metabolism and excretion (ADME). It determines change of ADME processes
with time.
Absorption:-is defined as the process by which a drug proceeds from the
site of administration to the site of measurement (usually blood, plasma or
serum)
Distribution:-is the process of reversible transfer of drug to and from the
site of measurement (usually blood or plasma)
Metabolism:-is the process of a conversion of one chemical species to
another chemical species
Excretion:-is the irreversible loss of a drug in a chemically unchanged or
unaltered form
Fig:-ADME Process

4. Pharmacodynamics:-refers to the relationship between the drug concentration at
the site of action (receptor) and pharmacological response, including biochemical
and physiologic effects that influence the interaction of drug with the
receptors. Thus, it represents the mechanisms of drug actions and their
pharmacological effects.
For a drug to be absorbed and distributed into organs and tissues and eliminated
from the body, it must pass through one or more biological membranes/barriers at
various locations. Thus, the nature of the gastrointestinal barrier is of
considerable importance in drug absorption.
Nature : Cell membranes are semipermiable membranes act as a selective barrier
to the passage of molecules. Water, some selected small molecules )amino acids,
sugars, fatty acids) and lipid soluble molecules pass through such membranes,
whereas highly charged molecules and large molecules such as protein and protein
bound drugs, do not.
Chemistry : Complex structure composed of phospholipids, proteins and
carbohydrates.
Thickness : 70 - 100 Ǻ
Structure : Two theories regarding structure of cell membrane
Membrane
Physiology

5. Fig:-Plasma Membrane
“The process of movement of drug from its site of administration to
systemic circulation” is called as absorption.
There three broad categories are
1. Transcellular / intracellular transport
A. Passive Transport Processes
I. Passive diffusion
II. Pore transport
III. Ion- pair transport
Gastrointestinal Absorption of Drug
Mechanism of Drug Absorption

6. IV. Facilitated or mediated diffusion
B. Active transport processes
I. Primary
II. Secondary
a. Symport (Co-transport)
b. Antiport (Counter transport)
2. Paracellular / Intercellular Transport
A. Permeation through tight junctions of epithelial cells
B. Persorption
3. Vesicular or Corpuscular Transport (Endocytosis)
A. Pinocytosis
B. Phagocytosis
Fig:-Mechanism of Drug Absorption

7. Passive Diffusion:-Also called non-ionic diffusion, it is the major process for
absorption of more than 90% of the drugs. The driving force is concentration or
electrochemical gradient. It is defined as the difference in the drug concentration
on either side of the membrane.
Fig:-Passive Transport
Passive diffusion is best expressed by Fick’s first law of diffusion, which states
that the drug molecules diffuse from a region of higher concentration to one of
lower concentration until equilibrium is attained and that the rate of diffusion is
directly proportional to the concentration gradient across the membrane.
Passive Diffusion

8. Here,
dQ/dt = rate of drug diffusion.
D= diffusion coefficient of the drug.
Km/w = partition coefficient of the drug between membrane and
the aqueous phase
(CGIT – C) = difference in the concentration of drug in GI fluid & the plasma
h= thickness of the membrane (length)
 It is also called as convective transport, bulk flow or filtration.
 The driving force is hydrostatic pressure or the osmotic differences across the
membrane.
 The process is important in the absorption of low molecular weight (less than
100), generally water-soluble drugs through narrow, aqueous-filled channels
ex: urea, water and sugars.
Fig:-Water Soluble Drug
Pore Transport (Filtration)

9. Strong electrolyte drugs maintain their charge at all physiological PH
values
and penetrate the membrane very poorly. When the ionized drug is linked
up with an oppositely charged ion, an ion pair is formed in which the overall
charge is neutral and this neutral drug complexes diffuses more easily across
the membrane.
Absorption of drugs like quaternary ammonium compounds and sulphonic
acids, which ionised under all pH conditions, is ion-pair transport.
Despite their low o/w partition coefficient values, such agents penetrate the
membrane by forming reversible neutral complexes with endogenous ions of
the GIT like mucin.
Such neutral complexes have both the required lipophilicity as well as
aqueous solubility for passive diffusion. Such a phenomenon is called as
ion-pair transport.
Propranolol, a basic drug that forms an ion pair with oleic acid, is absorbed
by this mechanism.
Examples - Quaternary ammonium compounds, tetracyclines.
Ion pair Transport

10. Fig:-Ion pair Transport of Cationic Drug
It is a carrier-mediated transport system that operates down the concentration
gradient (downhill transport) but at a much a faster rate than can be accounted by
simple passive diffusion. The driving force is concentration gradient (hence a
passive process). Since no energy expenditure is involved, the process is not
inhibited by metabolic poisons that interfere with energy production. Example: Fat
soluble vitamin, Tetracycline
This system is carrier mediated so it is saturable and structurally selective
for the drug and shows competitive kinetics for drugs of similar structures
This is a very minor process of drug transport.
Facilitated Diffusion

11. Fig:-Facilitate diffusion of vit B12
Active transport is a carrier mediated process that involve the transfer of drug
against a concentration gradient that is from a region of low concentration to
region of high drug concentration. Therefore, this is energy consuming system that
is chemical energy is needed. In this process, a carrier binds with the drug to form
a carrier drug complex that shuttles the drug across the membrane and then
dissociates the drug on the other side of the membrane.
Active transport mechanisms are further subdivided into –
Primary active transport:-
In this process, there is direct ATP requirement. Moreover, the process transfers
only one ion or molecule and in only one direction, and hence called as uniporter
e.g. absorption of glucose.
Active Transport

12. Secondary active transport:-
In these processes, there is no direct requirement of ATP i.e. it takes advantage of
previously existing concentration gradient. 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 in the opposite direction. Accordingly this process
is further subdivided into –
Symport )co-transport) – involves movement of both molecules in the
same direction e.g. Na+
-glucose symporter
Antiport )counter-transport) – involves movement of molecules in the
opposite direction e.g. H+
ions using the Na+
gradient in the kidneys

13. Fig:-Active Transport
The major substances that are believed to be actively transported are:-
 Sodium, other ions such as calcium & iron
 Body nutrients sugars (glucose, galactose), amino acids
 Vitamins (riboflavin, thiamine, pyridoxine)
 Drug molecules (5-flurouracil, methyldopa, nicotine)

14. “Drug absorption by active transport follows both first order and zero order
rate kinetic”
Vesicular transport is the process of engulfing particles or dissolved materials by
cell.
 Pinocytosis:- refers to the engulfment of small solutes
 Phagocytosis:- refers to the engulfment of larger particles of
macromolecules generally by macrophages
During pinocytosis or phagocytosis, the cell membrane invaginates to surround the
material and then engulf the material, incorporating it into the cell. Subsequently,
the cell membrane containing the material form a vesicles or vaculoes within the
cell.
Vesicular Transport

15.  Exocytosis - moving out of the cell.
 Endocytosis - moving into the cell.
Fig:-Phagocytosis Fig:-Pinocytosis
This phenomenon is responsible for the cellular uptake of macromolecular
nutrients like fats and starch, oil soluble vitamins like A, D, E and K and drugs
such as insulin. Another significance of such a process is that the drug is
absorbed into the lymphatic circulation thereby bypassing first-pass hepatic
metabolism.

16. 1.Katzung, Bertram G. 2012. Basic & Clinical Pharmacology. 12th. New york :
Lange Medical Publications, 2012. p. 449.
2.Tripathi, KD. 2019. Essentials of Medical Pharmacology. 8th. New Delhi :
Jaypee Brothers Medical Publishers, 2019. pp. 15-27. ISBN:978-93-5270-499-6.
3.YU, Leon Shargel.Susanna Wu-Pung.Andrew. 2012. Applied Biopharmaceutics &
Pharmacokinetics. 6th. s.l. : McGraw-Hill, 2012. pp. 131-150. ISBN-13:978-007-
160393-5.
4.https://www.google.com/search?q=active+transport&rlz=1C1CHBD_enBD920B
D920&sxsrf=ALeKk037l76crga9ldbghNdboW1XG_eAsg:1614685422485&sourc
e=lnms&tbm=isch&sa=X&ved=2ahUKEwiB15_4w5HvAhXh7HMBHW5pAwM
Q_AUoAXoECBIQAw&biw=1366&bih=600
5. https://www.slideshare.net/SURYAKANTVERMA2/biopharmaceutics-
mechanisms-of-drug-absorption
Bibliography