BIOPHARMACEUTICS 1

PHS 3204
INDUSTRIAL PHARMACY
2018

Biopharmaceutics 1
Scope of this Biopharmaceutics Course
• How drugs exert their therapeutic effect
• ADME
• Why a blood drug concentration – time profile is an
acceptable means to describe drug concentration at
the site of action
• How formulation strategies can be employed to
modify drug absorption, distribution, metabolism and
excretion
• Bioavailability, bioequivalence and its relevance
• Drug Half-Life
Biopharmaceutics 2
 Objectives
• Overview of how drug exerts its action
• Define Biopharmaceutics
• Define ADME
• Explain the factors that influence ADME processes
• Define Bioavailability and differentiate between
absolute and relative bioavailability
• Explain modification of drug ADME by formulation
• Identify the processes occurring at different points of
the blood concentration –time curve
• Define Pharmacokinetics and the drug’s half life
Biopharmaceutics 3
 INTRODUCTION
Drugs: are pharmacologically active agents
• Are used in the diagnosis, prevention, mitigation, cure
and treatment of disease conditions
• Are presented and administered to the patient in a
variety of dosage forms or drug delivery systems :
tablets, capsules, injections, ointments, creams,
aerosols, etc. for their local action or systemic effects
• When administered they release and deliver drug to
the site of action to exert the desired therapeutic effect
• Are tailored to meet the patient’s needs: safety,
appropriateness, convenience/acceptance.
Biopharmaceutics 4
 INTRODUCTION
• Drug product performance : refers to the release of
drug substance from the drug product either for
local drug action or drug absorption into plasma for
systemic therapeutic action.
• The Observed effect of a drug: is the inherent
pharmacological activity of the drug + its ability to
reach the receptor site in appropriate concentration
• The focus is to develop quality drug products, that
are safer, therapeutically more effective and more
convenient for the patient

Biopharmaceutics 5
 INTRODUCTION
Drugs elicit a response by:
 Occupying a receptor site (e.g. macromolecules in a particular
tissue)
 Altering or interfering with the body’s homeostatic mechanisms
(e.g. stimulation of secretion of an endogenous compound)
• Drug should be distributed within the body in order to act,
compared to drugs that exert a local action (topical)
• Treatments involve the transfer of drug from the site of
administration to its site of action
• Transfer of drug utilizes the systemic circulation and/or the
lymphatic system to the drug receptor or site of action
• Routes of drug administration include: oral/ GIT, muscle and
subcutaneous tissues, the lungs, the body orifices, etc.

Biopharmaceutics 6
 INTRODUCTION
• Drug product performance : refers to the release of
drug substance from the drug product either for local
drug action or drug absorption into plasma for
systemic therapeutic action.
• The Observed effect of a drug: is the inherent
pharmacological activity of the drug + its ability to
reach the receptor site in appropriate concentration
• The focus of dosage formulation therefore is to
develop quality drug products, that are safer,
therapeutically more appropriate and effective and
more convenient for the patient
Biopharmaceutics 7
 INTRODUCTION
The goal of drug therapy is to deliver the
right drug,
– in the right concentration,
– to the right site of action,
– for the right duration of time,
– to produce the desired therapeutic
effect

Biopharmaceutics 8
 How drugs act
Drugs elicit a response by:
 Occupying a receptor site (e.g. macromolecules in a particular
tissue)
 Altering or interfering with the body’s homeostatic mechanisms
(e.g. stimulation of secretion of an endogenous compound)
• Drug have to be distributed within the body in order to act
systemically, as opposed to drugs that exert a local action
(topical)
• Drug treatments involve the transfer of drug from the site of
administration to its site of action
• Transfer of drug utilizes the blood circulation and/or the
lymphatic system to the drug receptor or site of action
• When a drug produces an effect, it is interacting at a molecular
level with cellular structures/material
Biopharmaceutics 9
 Agonists and antagonists
Drug molecules that bind to a receptor and
cause a reaction that:
– stimulates cellular functions are agonists
• Activate receptors to a higher response
– Inhibits cellular functions are antagonists
• Block the action of the receptor

Biopharmaceutics 10
 Sequence of events upon drug administration

• Drug in a specific delivery system is administered to patient via

specific route
• Drug is released from a delivery system in a predictable and
determinable manner
• Some fraction of drug from the site of administration into the
surrounding tissue and/or into systemic circulation
• Drug reaches its site of action (receptor)
• A pharmacologic response is elicited when the concentration
of drug reaches the minimum effective concentration (MEC)
• Dosing regimen: (starting dose, maintenance dose, dosage
form, dosing interval,) that is therapeutically effective in the
majority of patients is determined in a clinical trial
– Influences the concentration-time profile of a drug in the body and
thus the duration of therapeutic action
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 ADME
Stands for the pharmacokinetic processes of:
• Absorption
• Distribution
• Metabolism
• Excretion

Biopharmaceutics 12
 Absorption
• Absorption: is the process of transfer of drug
molecules from the site of administration to
the blood or lymphatic system traversing
across membranes.
• Only drug injected directly into the vein does
not require absorption.

Biopharmaceutics 13
 Drug Disposition
• Are the processes that follow drug absorption
(distribution and elimination)
– Distribution: is the process by which drug is
transported away from the region of
administration via systemic circulation and by
diffusion into tissues and fluids of the body.
– Elimination processes: These are processes that
reduce the amount of drug in the body and
terminate drug action: metabolism and excretion

Biopharmaceutics 14
 Sequence of events upon drug administration

• Drug in a specific delivery system is administered to patient via

specific route
• Drug is released from a delivery system in a predictable and
determinable manner
• Some fraction of drug from the site of administration into the
surrounding tissue and/or into systemic circulation
• Drug reaches its site of action (receptor)
• A pharmacologic response is elicited when the concentration
of drug reaches the minimum effective concentration (MEC)
• Dosing regimen: (starting dose, maintenance dose, dosage
form, dosing interval,) that is therapeutically effective in the
majority of patients is determined in a clinical trial
– Influences the concentration-time profile of a drug in the body and
thus the duration of therapeutic action
Biopharmaceutics 15
Factors that influence time course of drug
in blood
• The physico-chemical properties of a drug
• Type of dosage form in which drug is administered
• The excipients used and method of manufacture of the dosage
form
• The size of dose and frequency of dosing
• The site of absorption of drug
• Co-administration of other drugs
• Type of food taken by patient
• The disease state
• The age of the patient
• The genetic make-up of the patient
Biopharmaceutics 16
Biopharmaceutics Key Definitions

KEY DEFINITIONS

Biopharmaceutics 17
 Biopharmaceutics
Concerns the interrelationship between the
– physical and chemical properties of the drug,
– the dosage form in which it is delivered
and
– the route of administration,
on the rate and extent of systemic drug
absorption

Biopharmaceutics 18
 Biopharmaceutics
• Is the study of factors that influence the
presence of drug at the site of absorption and
the transfer of the dissolved drug across
biological membranes into systemic circulation
• Is the application of the knowledge of the
release and transport of drug across bio-
membranes to obtain/build in or predict
therapeutic outcome from a product upon
administration to a patient
Biopharmaceutics 19
 Bioavailability
• Refers to the rate and extent at which the active moiety (drug or
metabolite) enters circulation and thereby accesses the site of action
• Is the rate at which the drug becomes available to the body and the
extent to which the dose is ultimately absorbed after administration of
a particular pharmaceutical form.
• Is dependent upon the properties of dosage form; i.e. the design and
manufacture of the formulation from which the drug is released
– Poor or inappropriate formulation results in a product that releases drug too
slow or fails to release a portion of the drug or leads to undesired variations in
performance of individual units
 excipient -components greatly influence rate of release of drug from a
formulation: both slow and fast rates of absorption can be desirable
depending on specific therapeutic goals
– The factors that influence the process of dissolution of drug in a dosage form
especially for particulate drug affect bioavailability
Differences in bioavailability between formulations of the same drug can have
clinical significance
Biopharmaceutics 20
 Key Parameters
• Minimum Effective Concentration(MEC):
• Onset of drug action/Onset time: t0
• Cmax = Peak concentration
• tmax = peak time
• Intensity of action
• Area under curve (AUC)
• Minimum toxic concentration (MTC)

Biopharmaceutics 21
 Key Parameters ctd.
• Duration of therapeutic action
• Therapeutic range: sub-therapeutic, toxic levels
• Maximum Safe Therapeutic Concentration:
(MSC)
• Absorption Phase
• Elimination phase
• Absorption process in equilibrium with
elimination process

Biopharmaceutics 22
A typical blood plasma drug concentration-
time curve (oral admin)
https://1.bp.blogspot.com/-gb1DRJlFUKM/UmBMmZ5FLAI/AAAAAAAAAes/ktF967EFlOs/s1600/Screen+shot+2013-10- 17+at+4.45.57+PM.png

Biopharmaceutics 23
Blood plasma drug concentration –time curve following
administration IV and 3 oral dosage forms
https://www.boomer.org/c/p4/c20/Fig2012.jpg

Biopharmaceutics 24
 Drug Absorption
• Mechanism of drug transport
– Passive diffusion
– Facilitated transport
– Active transport
– Filtration
– pinocytosis
• Drug absorption via different routes of administration
– GIT
– Buccal cavity/sublingual
– Rectum
– Lungs
– injection sites
– skin

Biopharmaceutics 25
 Factors influencing drug absorption
• Physiological Factors
• Physicochemical factors of drug
• Formulation/dosage form factors

Biopharmaceutics 26
 Physiological factors
Nature of the cell membrane
• Semi-permeable membranes: permit only
water, small molecules and lipid soluble
molecules
• Highly charged molecules and large molecules
like proteins and protein bound drug can not
cross

Biopharmaceutics 27
 Physico-chemical Properties
• Drug solubility
• Surface area of drug
• State of hydration
• Salt form of drug
• Amorphous or crystalline

Biopharmaceutics 28
 Dosage form factors
• Type and nature of dosage form : solid, liquid,
emulsion, suspension, solution, etc.
• Excipients used in dosage form: diluents,
surfactants, lubricant, etc.
• Route of administration: oral, injectable,
topical, etc.

Biopharmaceutics 29
 References
• PHARMACEUTICS. The science of Dosage form
design: M. E. Alton, Editor, 1999.
• THE PHARMACEUTICAL CODEX, Principles and
Practice of Pharmaceutics, 12th Edition.1994
• Biopharmaceutics and Clinical
Pharmacokinetics, Milo Gibaldi; 1977.

Biopharmaceutics 30