Biopharmaceutics

1 By: Merga D.
 Outline
2

 Introduction
 Barriers of drug
transport
 Mechanisms of drug
transport

By: Merga D.
 Learning outcomes
3

 Upon successful completion of this session, the

student will be able to:
 Define Biopharmaceutics
 Identify barriers of drug transport
 Mechanisms of drug transport

By: Merga D.
 Introductory activity
4

 What is Pharmaceutics?
 discipline of pharmacy that deals with all
aspects of the process of turning a new
chemical entity into a medication able to be
safely and effectively used by patients
 put at its most simplistic, it converts a

drug into a medicine

By: Merga D.
 Introduction…
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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

By: Merga D.
 Introduction…
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 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
By: Merga D.
 Introduction…
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 Drugs may be given by

 parenteral

 enteral
 Other route (transdermal, inhalation, intranasal

Ophthalmic)
for systemic absorption

By: Merga D.
 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

By: Merga D.
 Introduction…
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Clinical
IV effect
E
injection Drug at site (s) L Unchanged
of action I drug
A M excreted
B I
DISTRIBUTIO
S N N
O A
Drug at site R
Bound unbound T
of P
administration drug drug I
T O metabolis
(extravascular)
I N m
O DISTRIBUTIO
N N Metabolites
excreted
Fig.: Drug ADME Drug in tissues (including
blood cells) & other fluid of
By: Sintayehu distribution
By: Merga D.
A 6/29/2021
 Introduction…
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 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

By: Merga D.
 Introduction…
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By: Merga D.
 Introduction…
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 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

By: Merga D.
 Introduction…
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 For extravascularly administered drug to be 100%

bioavailable, a drug must be
 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

By: Merga D.
 Introduction…
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 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

By: Merga D.
 Introduction…
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 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

By: Merga D.
 Introduction…
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 The study and characterization of the time course of

drug (ADME) is termed pharmacokinetics

By: Merga D.
 Introduction…
17 Bioavailability of drug may be influenced by many
factors

 Physicochemical properties  Site(s) of absorption

of drug  Food
 Type of Dosage form  Disease state
 Dose and frequency of  Co-administration
administration  Age of patient
 Route of administration
A
Others
By: Merga
Sintayehu
D. 6/29/202
1
 Introduction…
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 Factors affecting BA can broadly grouped

into:
 Biological/Physiological factors
 Physicochemical factors
 Dosage form factors

By: Merga D.
 Introduction…
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 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

By: Merga D.
 Barriers to Drug Transport

20 By: Merga D.
 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

By: Merga D.
 Barriers to Drug Transport…
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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
By: Merga D.
 Barriers to Drug Transport…
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 The barrier has the

characteristics of a
semipermeable membrane,
 allowing the rapid transit of
some materials
 impeding or preventing the
passage of others

By: Merga D.
 Barriers to Drug Transport…
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Epithelia
 Epithelia are a collection of cells

 They line most body surfaces

 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
By: Merga D.
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Epithelia…
 There are several morphologically distinct

common epithelial types

 Simple squamous epithelium
 Simple columnar epithelium
 Transitional epithelium
 Stratified squamous epithelium

By: Merga D.
 Barriers to Drug Transport…
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Simple squamous epithelium

 This forms a thin layer of flattened

cells and consequently is relatively

permeable
 Sites

 most of the blood vessels

 lung alveoli
 Function
 Diffusion,filtration
 Secretion and absorption

By: Merga D.
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Simple columnar epithelium

 A single layer of columnar cells

attached to the basement membrane

 Sites

 Lines the stomach, SI, LI

 Function
 absorption

 secretion

By: Merga D.
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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
 Sites

 lines the organs of the urinary system

By: Merga D.
 Barriers to Drug Transport…
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Stratified squamous epithelium

 Consists of many cells arranged in

layers
 Site

 Lines mouth, oesophagus, the

vagina
 Function

 Protection against abrasion

 Barrier to infection

By: Merga D.
 Barriers to Drug Transport…
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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 DD process

By: Merga D.
 Mechanisms of drug transport

31 By: Merga D.
 Mechanisms…
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 There are two main mechanisms of drug transport

across the gastrointestinal epithelium:
 Trans-cellular
 Para-cellular

Fig. Mechanisms of absorptive

By: Merga D.
 Mechanisms…
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 The trans-cellular pathway is further divided into

 Simple passive diffusion
 Carrier-mediated transport
 Endocytosis

By: Merga D.
 Mechanisms…
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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

By: Merga D.
 Mechanisms…
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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

By: Merga D.
 Mechanisms…
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Trans-cellular pathways…
 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

By: Merga D.
 Mechanisms…
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Fig: Active transport of a drug aBy:ByMerga

c: SrD.inotasyeshuaA
 Mechanisms…
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Trans-cellular pathways…
 Facilitated diffusion:
 Drugs are transported down the concentration gradient
 does not require an energy
 butdoes require a concentration
gradient

By: Merga D.
 Mechanisms…
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Trans-cellular pathways…
 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
 primary mechanism of transport of macromolecules
By: Merga D.
 Mechanisms…
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Trans-cellular pathways…
 Endocytosis can be further subdivided into four main
processes:
 pinocytosis
 receptor-mediated endocytosis

 phagocytosis

 transcytosis

By: Merga D.
 Mechanisms…
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Trans-cellular pathways…
 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

By: Merga D.
 Mechanisms…
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Trans-cellular pathways…
 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
By: Merga D.
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Trans-cellular pathways…
 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

By: Merga D.
 Mechanisms…
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Trans-cellular pathways…
 Transcytosis
 the process by which the material internalized by the
membrane domain is transported through the
cell and secreted on the opposite side

By: Merga D.
 Mechanisms…
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By: Merga D.
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 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

By: Merga D.
 Mechanisms…
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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

By: Merga D.