Lecture 1-1.pdf

Biopharmaceutics
8/11/2020
By: Sintayehu A
1

Outline
 Introduction
 Barriers of drug transport
 Mechanisms of drug transport
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Introduction
3
Biopharmaceutics
 a branch of pharmaceutical sciences that concerns the
interrelationship b/n
the physicochemical properties of a drug
the dosage form in which the drug is given
the route of administration
on the rate and extent of systemic drug absorption
8/11/2020
By: Sintayehu A

Introduction…
 For a drug to be effective,
enough amount needs to reach its site(s) of action
stay at site(s) of action long enough
 This depends upon;
the route of administration
the form in which it is administered
the rate at which it is delivered
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By: Sintayehu A
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Introduction…
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 Drugs may be given by
 parenteral
 enteral
 percutaneous (transdermal)
 inhalation and intranasal
for systemic absorption

Introduction…
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 In intravenous route,
 a drug is introduced directly into the bloodstream
 complete (100%) systemic drug availability
 All other routes of administration involve the
absorption of the drug into the blood from the ROA
 does not guarantee that the whole dose will reach
systemic circulation intact

Introduction…
By: Sintayehu A
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Fig.: Drug ADME
Drug at site of
administration
(extravascular)
DISTRIBUTION
A
B
S
O
R
P
T
I
O
N
IV injection E
L
I
M
I
N
A
T
I
O
N
Unchanged
drug
excreted
Drug in tissues (including blood
cells) & other fluid of distribution
Bound drug unbound drug
Clinical effect
Metabolites excreted
DISTRIBUTION
Drug at site (s) of
action
metabolism
8/11/2020

Introduction…
 The relative amount of drug that reaches the systemic
circulation intact and the rate at which this occurs is
known as bioavailability
 Bioavailability is therefore defined as the rate and extent
of drug absorption
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Introduction…
9
 it is often difficult to access the drug at its site(s) of
action
 its concentration in the plasma is often taken as a
surrogate for its concentration at its site(s) of action
 Unbound drug in the plasma would give a better
estimate of the concentration of the drug at its site(s)
of action
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By: Sintayehu A

Introduction…
 For extravascularly administered drug to be 100%
bioavailable,
 completely released from DF
 fully dissolved in body fluids
 stable in solution in body fluids
 pass through physiologic barriers into surrounding
circulation without metabolism
 reach into systemic circulation intact
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By: Sintayehu A
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Introduction…
 Whenever a drug is administered by any non-vascular
route, rapid and complete absorption into bloodstream is
sought:
 there is relationship between drug concentration in body and
magnitude of therapeutic response
 the greater concentration achieved, the greater magnitude
of response
 it is desired to obtain these concentrations rapidly
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By: Sintayehu A
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Introduction…
 The concentration of the drug in blood plasma
depends on numerous factors
 These include,
 the amount of an administered dose that is absorbed and
reaches the systemic circulation;
 the extent of distribution of the drug b/n the systemic
circulation and other tissues and fluids;
 the rate of elimination of the drug from the body
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By: Sintayehu A
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Introduction…
 The study and characterization of the time course of
drug ADME is termed pharmacokinetics
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Introduction…
 Physicochemical properties
of drug
 Type of Dosage form
 Dose and frequency of
administration
 Route of administration
 Site(s) of absorption
 Food
 Disease state
 Co-administration
 Age of patient
 Others
Bioavailability of drug may be influenced by many factors
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By: Sintayehu A

Introduction…
 Factors affecting BA can broadly grouped into:
 Biological/Physiological factors
 Physicochemical factors
 Dosage form factors
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By: Sintayehu A
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Introduction…
 Emphasis is on factors influencing oral drug absorption
 Oral route is most popular route of drug administration
 The vast majority of drug dosage forms are designed for
oral ingestion:
 Natural and convenient route
 Relatively easy to manufacture
 need not be sterilized, compact, produced in bulk
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Barriers to Drug Transport
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Barriers to Drug Transport…
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 The cytoplasm is held as an intact unit by a cell
membrane,
 which surrounds it and prevents it from mixing with its
surroundings
 allow penetration of some substances and not
others
 selectively permeable
 acts as a permeability barrier

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 Organs and tissues are collections of cells
surrounded by specialized cell structures called
epithelia,
 which can be thought of as the organ’s ‘outer
membrane’ in an analogous fashion to the membrane
that surrounds the individual cell
 Like cell membranes, epithelia are the site for a
wide range of transport, barrier and secretory
processes

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 In order for a drug to reach a site of action,
 it must pass from an external site to an internal
site
 pass through a number of tissues and epithelia
 Overcoming these barriers to absorption is one of the
most important considerations in the drug delivery
process

 The barrier has the characteristics of a
semipermeable membrane,
allowing the rapid transit of some materials
impeding or preventing the passage of others
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By: Sintayehu A
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Epithelia
 With a few exceptions, all internal and external body
surfaces are covered with epithelium
 This consists of a layer of structural protein, normally
collagen, called the basal lamina, on
which sit one or more layers of epithelial cells

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Epithelia…
 There are several morphologically distinct common
epithelial types
 Simple squamous epithelium
 Simple columnar epithelium
 Transitional epithelium
 Stratified squamous epithelium

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Simple squamous epithelium
 This forms a thin layer of flattened cells and
consequently is relatively permeable
 This type of epithelium lines most of the blood
vessels

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Simple columnar epithelium
 A single layer of columnar cells is found in the
epithelium of organs such as the stomach and small
intestine

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Transitional epithelium
 This is composed of several layers of cells of
different shapes and it lines epithelia which are
required to stretch

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Stratified squamous epithelium
 These membranes are several cells thick and are
found in areas which have to withstand large
amounts of wear and tear, e.g. the inside of the
mouth and oesophagus and the vagina

Mechanisms of drug transport
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Mechanisms…
 There are two main mechanisms of drug transport
across the gastrointestinal epithelium:
 Trans-cellular
 Para-cellular
Fig. Mechanisms of absorptive
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Mechanisms…
 The trans-cellular pathway is further divided into
 Simple passive diffusion
 Carrier-mediated transport
 Endocytosis
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By: Sintayehu A
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Mechanisms…
Trans-cellular pathways
 Passive diffusion:
 transport for relatively small lipophilic molecules
 many drugs transported via this route
 drug molecules pass across cell membrane via a region
of high concentration to a region of lower concentration
 i.e. from lumen to blood
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Mechanisms…
Trans-cellular pathways…
 Carrier-mediated transport:
 The drug require carrier or transporter to cross
membrane
carrier-mediated transport
 Two main types carrier-mediated transport
Active transport and
Facilitated diffusion
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By: Sintayehu A
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Mechanisms…
 Active transport: materials transported against a
concentration gradient
 active transport is an energy consuming process
 A carrier or membrane transporter is responsible for
binding a drug and transporting it across the membrane
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Mechanisms…
Fig: Active transport of a drug across a cell membrane
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By: Sintayehu A
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Mechanisms…
 Facilitated diffusion:
 Drugs are transported down the concentration gradient
 does not require an energy
but does require a concentration gradient
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By: Sintayehu A
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Mechanisms…
 Endocytosis:
 Endocytosis is the process by which the plasma membrane
of the cell invaginates and the invaginations become
pinched off, forming small intracellular membrane-bound
vesicles that enclose a volume of material
 Thus material can be transported into the cell
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By: Sintayehu A
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Mechanisms…
 Endocytosis can be further subdivided into four main
processes:
 pinocytosis
 receptor-mediated endocytosis
 phagocytosis
 transcytosis
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By: Sintayehu A
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Mechanisms…
 Pinocytosis:
 the engulfment of small droplets of extracellular fluid by
membrane vesicles
 The cell will internalize material regardless of its metabolic
importance to that cell
 The fat-soluble vitamins A, D, E and K are absorbed via
pinocytosis
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By: Sintayehu A
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Mechanisms…
 Receptor-mediated endocytosis
 Many cells within the body have receptors on their cell
surfaces that are capable of binding with suitable ligands to
form ligand-receptor complexes on the cell surface
 These complexes cluster on the cell surface and then
invaginate and break off from the membrane to form
coated vesicles
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Mechanisms…
 Phagocytosis Phagocytosis
 can be defined as the engulfment by the cell membrane
of particles larger than 500 nm.
 This process is important for the absorption of polio
and other vaccines from the gastrointestinal tract
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By: Sintayehu A
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Mechanisms…
 Transcytosis
 the process by which the material internalized by the
membrane domain is transported through the cell and
secreted on the opposite side
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Mechanisms…
 Para-cellular pathway
 transport of materials in the aqueous pores b/n the cells
 transport ions such as calcium and for the transport of
sugars, amino acids and peptides at concentrations above
the capacity of their carriers
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Mechanisms…
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By: Sintayehu A
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Efflux of drugs from the intestine
 there are counter-transport efflux proteins that expel
specific drugs back into the lumen of the GIT after they
have been absorbed
 efflux have a detrimental effect on drug BA
 One of the key counter-transport proteins is P-
glycoprotein

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Lecture 1-1.pdf