Transcript BIOPHARMACEUTICS

BIOPHARMACEUTICS, NEW
DRUG DELIVERY SYSTEMS
& DEVICES
A. S. Adebayo, Ph.D.
7/20/2015
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BIOPHARMACEUTICS
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COURSE CODE:
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LEVEL:
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DURATION:
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CREDIT VALUE:
7/20/2015
PPHAR2213
2
4 HOURS/week
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COURSE DESCRIPTION
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Biopharmaceutics course seeks to educate and train
candidates in the principles underlining drug
absorption, distribution, metabolism and excretion
(ADME) following its administration to human or
animal subjects.
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The course places emphasis on the dependence of
drug absorption on the physical and chemical
nature of drug substances, the effect of dosage
form in which it is designed and the factors related
to the physiologic and pathologic conditions of the
subjects to which it is administered.
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COURSE DESCRIPTION (Cont.)
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The aim is to develop in the candidate the ability
to integrate all these factors holistically in
optimizing therapeutic benefit to the patient while
minimizing adverse or untoward effects of
medicinal products.
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In addition, the course would train the candidates
in novel delivery technologies that are currently
being employed for enhancing drug delivery to
various targets in the body.
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OBJECTIVES
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On completion of the course the student should be able to:
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Discuss factors that influence absorption, distribution,
metabolism and excretion of the drugs in the body.
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Explain how dosage forms and presentations may affect
the delivery of drug substances to various parts of the
body, particularly the site of action
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Explain the concepts of bioavailability, bioequivalence and
drug products selection and substitution.
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COURSE OBJECTIVES (Cont.)
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Describe the drug interactions, which occur
during absorption, distribution and elimination
of drugs and how these interactions influence
the therapeutic effects of particular drugs.
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Describe the features and explain the design
and mechanisms of drug delivery via some
novel delivery systems.
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BIOPHARMACEUTICS
GENERAL OVERVIEW
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General Overview/Definitions
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Biopharmaceutics is concerned with the relationship between the
physicochemical properties of a drug in a dosage form and the
observed therapeutic response after its administration.
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Biologic response
 Expressed as the alteration of the biologic process existing
before the drug was administered
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Its magnitude is related to the concentration of drug reaching
the receptor site.
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The observed biological effect of drug in a dosage form =
inherent pharmacological activity of the drug + its ability to
reach the receptor site in appropriate concentration + MRT
Thus, the onset, intensity and duration of therapeutic effect of
most drugs depend on factors of the biological system + the
dosage form.
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General Overview/Definitions
(Cont.)
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These factors play important role in:
 bringing the drug to the biological site in the
body in quantities required +
 sustaining it at that concentration for the
desired length of time +
 getting the drug out of the site after it has
performed the desired effect.
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Hence, the scope of biopharmaceutics is
comprised of the path the drug must take from
the dosage form to the site of action and the
factors encountered en-route.
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General Overview/Definitions
(Cont.)

Objectives of Biopharmaceutics course are to
gain a basic understanding of the processes of
drug absorption, distribution and elimination +
the potentials of dosage form effects on these
processes that can be applied to optimization of
therapeutic benefit for a patient.
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Dosage form of a drug exerts its major influence
on the absorption process, thus emphasis is
usually placed on drug absorption.
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Biopharmaceutics
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Biopharmaceutics simply means “the
effects of dosage form and route of
administration on the biological effect
of a drug”
-study of factors influencing the dissolution
of drug from dosage form into
biological fluids at the site of
absorption and the transfer of the
dissolved drug across biomembrane
into the systemic circulation.
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Biopharmaceutical methods
 The
application of knowledge
of drug release and transport
across
biomembrane
to
obtain
the
expected
therapeutic effect from a
product on administration to
a patient.
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Factors Influencing the time course of a
drug in plasma
 The
physical/chemical properties
of the drug
 Type
of dosage form of the drug
 Composition
and method of
manufacture of the dosage form
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Time-course of Drug in the Body
AROUND
IN
Mouth
Lungs
Rectum
Skin
Parenteral
OUT
Absorption
Distribution
oRBC
oPLASMA
PLASMA
PROTEIN
Metabolism
Excretion
oKidneys
oLungs
oSkin
oOthers
WATER
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Factors Influencing the time course of a
drug in plasma (Cont.)
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The size of the dose and frequency of
administration of the dosage form
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Site of absorption of the administered
drug
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Co-administration of other drugs
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Type of food taken by the patient
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Factors Influencing the time course of a
drug in plasma (Cont.)
 The
disease state of the patient that
may affect drug absorption,
distribution and elimination of the
drug
 The
age of the patient.
 The
genetic composition of the
patient
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Dosage form consideration
The
particle size of the drug
 Its
chemical nature e.g. salt, weak
acid or base, ester form, complex
form, etc.
 The
physical state of the drug e.g.
crystalline, amorphous, hydrate,
polymorphs, etc.
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Dosage form consideration (Cont.)
 The
inert ingredients e.g. diluents,
binders, disintegrants, suspending
agents, coating agent, etc.
 Type
of dosage form in the
traditional sense of it e.g. tablet,
capsule, solution, suspension,
suppository, etc.
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Bioavailability: rate & extent
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Bioavailability deals with the transfer of
drug from its site of administration into
the body system and this is manifested by
its appearance in general circulation.
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Because a transfer system is involved,
bioavailability is characterized by the rate
of transfer and the total amount
transferred.
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Factors Influencing Drug Absorption
 Can
be categorized into 3:
 Physiological
factors
 Physicochemical
 Dosage
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factors
form factors
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Schematic illustration of the steps involved in the appearance of intact drug in systemic circulation
following oral administration of a tablet
STOMACH (Gastric content.
pH 1-3)
SMALL INTESTINE (Intestinal
cont. pH 5-7)
Tablet
Tablet
Disintegration
Granules
Granules
Deaggregation
Fine
particles
Fine
particles
Dissolution
Dissolution
Drug in
solution
Drug in
solution
Absorption
Intact drug
Liver
Intact Drug in systemic
Circulation
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Intestinal metabolism
Hepatic
Metabolism
(1st Pass Effect)
Metabolites
Urine
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Pharmacologic effect
Rate limiting steps on systemic appearance of
drugs
Nature of Drug
Rate limiting step
Drug of very poor
Rate of dissolution in gastrointestinal fluid
aqueous solubility
Drug of high aqueous Rate at which drug crosses git membrane
solubility
Controlled-,
modified-, etc
release
formulation
Rate of release from the dosage form
Other general rate
limiting factors
Rate of gastric emptying into small intestine (e.g. enteric
coated tablets)
Rate at which drug is metabolized by the enzymes in the
intestinal mucosal cells en route into mesenteric blood
vessels
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Rate of metabolism of drug during its initial passage through
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the liver (i.e. First-pass effect).
Structure of the Gastro-intestinal Tract
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The g.i.t. consists of 3 anatomical regions:
Stomach
Small intestine
Large intestine (colon).
The small intestine comprises:
Duodenum
Jejunum
Ileum.
As a drug moves through these three regions, it
encounters different environments differing in pH, type of
enzymes, electrolytes, fluidity and surface features….. All
these can influence drug absorption.
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Anatomy of G.I.T
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Most significant sites of oral drug
absorption
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Anatomy of G.I.T.
The g.i.t. is basically a hollow muscular
tube composed of 4 concentric layers of
tissues, namely the:
 Mucosa (mucous membrane)
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Sub-mucosa
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Muscularis externa, and
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Serosa (the outermost layer, next to the
peritoneal cavity).
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The Mucosa
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Mucosa is the most important to drug absorption.
 It contains the cellular membrane through
which a drug must pass in order to reach the
blood (or lymph).
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The mucosa is itself made of 3 layers:
 Lining epithelium
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Lamina propria
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Muscularis mucosa
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Assignments
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Attempt a diagramatic illustration of the
gastrointestinal tract and clearly identify
the regions’ physiology by:
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pH
Volume of fluids
Length or duration of stay of ingested
substance
Thickness of the membranes
Blood supply
Enzyme presence & abundance.
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THANK YOU FOR YOUR
ATTENTION
BIOPHARMACEUTICS
Monday, 20 July 2015
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