Introduction to Bio

Pharmaceutics (Definitions
and Terminologies)

Dr Nyla Ajaz
Assistant Professor
Department of Pharmacy
The University of Faisalabad
• Drugs are substances intended for use in the
diagnosis, cure, mitigation, treatment, or
prevention of disease.
• Drugs are given in a variety of dosage forms or
drug products such as
• solids (tablets, capsules),
• semisolids (ointments, creams),
• liquids,
• suspensions,
• emulsions, etc, for systemic or local therapeutic activity
• Drug products can be considered to be drug
delivery systems that release and deliver drug
to the site of action such that they produce the
desired therapeutic effect.
• In addition, drug products are designed
specifically to meet the patient’s needs
including palatability, convenience, and safety.
 Introduction to Biopharmaceutics

• Biopharmaceutics:
• Biopharmaceutics examines the
interrelationship of the physical/ chemical
properties of the drug, the dosage form (drug
product) in which the drug is given, and the
route of administration on the rate and extent of
systemic drug absorption.
• Biopharmaceutics:
The importance of the drug
substance and the drug
formulation on absorption, and
in vivo distribution of the drug
to the site of action, is described
as a sequence of events that
precede elicitation/ production
of a drug’s therapeutic effect.
• First, the drug in its dosage form is taken by
the patient by an oral, intravenous,
subcutaneous, transdermal, etc, route of
administration.
• Next, the drug is released from the dosage
form in a predictable and characterizable
manner.
• Then, some fraction of the drug is absorbed
from the site of administration into either the
surrounding tissue for local action or into the
body (as with oral dosage forms), or both.
• Finally, the drug reaches the site of action.
Scheme demonstrating the dynamic relationship between the drug,
the drug product, and the pharmacologic effect.
 Drug product performance
• Drug product performance is defined as the
release of the drug substance from the drug
product either for local drug action or for drug
absorption into the plasma for systemic
therapeutic activity.
• Advances in pharmaceutical technology and
manufacturing have focused on developing
quality drug products that are safer, more
effective, and more convenient for the patient.
Drug product performance Parameters

1. Minimum effective concentration (MEC): The minimum

concentration of drug needed at the receptors to produce
the desired pharmacologic effect. A pharmacodynamic
response results when the drug concentration at the site of
action reaches or exceeds the MEC.
2. Minimum toxic concentration (MTC): The drug
concentration needed to just produce a toxic effect.
3. Onset time: The time required for the drug to reach the
MEC.
4. Duration of action: The difference between the onset time
and the time for the drug to decline back
The plasma level-time
curve is generated by
measuring the drug
concentration in plasma
samples taken at various
time intervals after a drug
product is administered.
• The concentration of
drug in each plasma
sample is plotted against
the corresponding time at
which the plasma sample
was removed
 Drug product performance Parameters
5 - The time of peak plasma level
(Tmax): The time of maximum
drug concentration in the plasma
and is proportional to the rate of
drug absorption.
6 - The peak plasma level
(Cmax): The maximum drug
concentration, usually related to the
dose and the rate constants for
absorption and elimination of the
drug.
7 - Area under the curve (AUC):
It is related to the amount of drug
absorbed systemically.
• Therapeutic window: Concentrations
between the MEC and the MTC.
Drugs with a wide therapeutic
window are generally considered
safer than drugs with a narrow
therapeutic window.
• Therapeutic index: Ratio between the
toxic and therapeutic doses
 Factors involved in Biopharmaceutics
• Biopharmaceutics involves factors that influence
(1) the design of the drug product,
(2) stability of the drug within the drug product,
(3) the manufacture of the drug product,
(4) the release of the drug from the drug product,
(5) the rate of dissolution/release of the drug at the
absorption site, and
(6) delivery of drug to the site of action, which may involve
targeting the drug to a localized area (eg, colon for Crohn
disease) for action or for systemic absorption of the drug.
 Drug disposition
• Drug disposition describes how drugs enter and exit
the body and explain how concentration in the body
change over time.
• Drug disposition: Drug distribution and elimination
• Four basic process explain the disposition of drugs
through the body:
1) Absorption
2) Distribution
3) Metabolism
4) Excretion
 Introduction to Biopharmaceutics ....

• Absorption: is the process of a substance entering the body. /

movement of drug from its site of administration to the
systemic circulation
• Distribution: is the dispersion of substances throughout the
fluids and tissues of the body/ movement of drug between one
compartment to and the other (generally blood and the
extravascular tissues)
• Metabolism (Biotransformation): is the irreversible
transformation of parent compounds into daughter
metabolites.
• Excretion: is the elimination of the substances from the body.
 Some Common Terms
• Bioavailability is the fraction of administered drug that
reaches the systemic circulation
• Bioavailability is expressed as the fraction of
administered drug that gains access to the systemic
circulation in a chemically unchanged form
• For example: If 100 mg of a drug are administered orally
and 70 mg of this drug are absorbed unchanged, the
bioavailability is 0.7 or seventy percent
• Bioavailable dose: The fraction of an administered dose
of a particular drug that reaches the systemic circulation
intact.
 Relative bioavailability
• Relative (apparent) bioavailability is the availability of the drug
from a drug product as compared to a recognized standard.
• The availability of drug in the formulation is compared to the
availability of drug in a standard dosage formulation, usually a
solution of the pure drug evaluated in a crossover study.
• The relative availability of two drug products given at the same
dosage level and by the same route of administration can be
obtained using the following equation;
• 𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝑎𝑣𝑎𝑖𝑙𝑎𝑏𝑖𝑙𝑖𝑡𝑦 = 𝐴𝑈𝐶𝐴 / 𝐴𝑈𝐶 B
A = the drug in the given formulation B = a recognized reference
standard
 Absolute Bioavailability
• The absolute bioavailability of drug is the systemic
availability of a drug after extravascular administration
compared to IV dosing.
• The absolute availability of a drug is generally measured by
comparing the respective AUCs after extravascular and IV
administration. This measurement may be performed as long
as VD and K are independent of the route of administration.
• Absolute availability after oral drug administration using
plasma data can be determined as follows
• 𝐴𝑏𝑠𝑜𝑙𝑢𝑡𝑒 𝑎𝑣𝑎𝑖𝑙𝑎𝑏𝑖𝑙𝑖𝑡𝑦 = 𝐹 = [𝐴𝑈𝐶]𝑃𝑂 × 𝐷𝑜𝑠𝑒𝐼𝑉/
[𝐴𝑈𝐶]𝐼𝑉 × 𝐷𝑜𝑠𝑒𝑃o
• Pharmacokinetics: Science of the kinetics of
drug absorption, distribution and elimination
(excretion and metabolism)
• Characterization of drug disposition is an
important parameter for determination and
modification of dosing regimes for individuals
and group of patients
• Pharmacokinetics involves both experimental
and theoretical approaches.
• Experimental: involves development of
biological sampling techniques, analytical
methods for measurement of drugs and
metabolites, procedure that facilitates data
collection and manipulation
• Pharmacokinetics involves both experimental
and theoretical approaches.
• Theoretical : involves development of
pharmacokinetic models that predicts drug
disposition after drug administration
• Pharmacodynamics: is the study of the biochemical
and physiological effects of drugs on the body; this
includes the mechanisms of drug action and the
relationship between drug concentration and effect.
• A typical example of pharmacodynamics is how a drug
interacts quantitatively with a drug receptor to produce
a response (effect).
• Receptors are the molecules that interact with specific
drugs to produce a pharmacological effect in the body.
 Toxicokinetics
• Application of pharmacokinetic principles to the
design, conduct, and interpretation of drug safety
evaluation studies and in validating dose-related
exposure in animals.
• Toxicokinetic data aid in the interpretation of
toxicologic findings in animals and extrapolation of
the resulting data to humans.
• Toxicokinetic studies are performed in animals during
preclinical drug development and may continue after
the drug has been tested in clinical trials
 Introduction to Biopharmaceutics ....
• Chemical Name:
Name used by the organic chemist to indicate
the chemical structure of the drug.
• Drug Product:
A finished dosage form, e.g., tablet, capsule, or
solution, that contains the active drug
ingredient, generally, but not necessarily, in
association with inactive ingredients
• Generic Name:
The established, non proprietary or common
name of the active drug in a drug product.
 Introduction to Biopharmaceutics ....

• Equivalence :-
It is a relative term that compares drug
products with respect to a specific
characteristic or function or to a
defined set of standards.
 Introduction to Biopharmaceutics ....

• Types of equivalence

Chemical Pharmaceutica
Equivalence l Equivalence

Bioequivalenc Therapeutic
e Equivalence
 Bioequivalent
• The property wherein two drugs with identical
active ingredients or two different dosage
forms of the same drug possess similar
bioavailability and produce the same effect at
the site of physiological activity.
 Introduction to Biopharmaceutics ....
Bioequivalence:
• It refers to the drug substance in
two or more identical dosage forms,
reaches systemic circulation at the
same rate and to the same relative
extent. i.e. their plasma
concentration-time profiles will be
identical without significant
statistical differences.
 Introduction to Biopharmaceutics ....

• When statistically significant

differences are observed in the
bioavailability of two or more drug
products, bio- inequivalence is
indicated.
 Introduction to Biopharmaceutics ....

Bioequivalent:
• Same drug (active ingredient or
chemical moiety)
• Same dose
• Same dosage
• Reaches to blood circulation with
same rate and same extent
 Introduction to Biopharmaceutics ....

• Chemical Equivalence :- It indicates that

two or more drug products contain the same
labelled chemical substance as an active
ingredient in the same amount.
• Pharmaceutical Equivalence :- This term
implies that two or more drug products are
identical in strength, quality, purity, content
uniformity and disintegration and dissolution
characteristics. They may, however, differ in
containing different excipients
 Introduction to Biopharmaceutics ....

• Pharmaceutical equivalents are the two

or more drug products are identical
in :The same therapeutically active
drug ingredient(s), same salt, ester, or
chemical form. The same dosage form.
Identical in strength, quality, purity,
content uniformity and disintegration
and dissolution and concentration and
route of administration.
 Introduction to Biopharmaceutics ....

Pharmaceutical equivalents may differ

in characteristics such as:
• Shape.
• Scoring configuration.
• Release mechanisms.
• Packaging.
• Excipients (including colors,
flavoring, preservatives)
 Introduction to Biopharmaceutics ....

• A generic drug product is considered

bioequivalent to the Reference (generally the brand
name) drug product if both products are
pharmaceutical equivalents and its rate and extent
of systemic drug absorption (bioavailability) do not
show a statistically significant difference when
administered:
• in the same dose of the active ingredient.
• in the same chemical form.
• in a similar dosage form.
• by the same route of administration.
• under the same experimental conditions.
 Introduction to Biopharmaceutics ....

• The generic drug product must be a

therapeutic equivalent to the Reference
drug product but may differ in certain
characteristics including
• shape,
• scoring configuration,
• packaging, and
• excipients (including colors, flavors,
preservatives, expiration date, and minor
aspects of labeling).
 Introduction to Biopharmaceutics ....

• Therapeutic Equivalence :-
This term indicates that two or more
drug products that contain the same
therapeutically active ingredient
elicit identical pharmacological
effects and can control the disease to
the same extent.
 Introduction to Biopharmaceutics ....

• Therapeutic equivalent drug products have

the following criteria:
• The products are safe and effective.
• The products are pharmaceutical
equivalents containing the same active drug
ingredient in the same dosage form, given
by the same route of administration, meet
compendial or other applicable standards of
strength, quality, purity, and identity, and
meet an acceptable in vitro standard.
• Pharmaceutical alternatives:
• are drug products that contain the same
therapeutic moiety but are different:
Salts, esters, or complexes (e.g.,
tetracycline hydrochloride versus
tetracycline phosphate).Dosage forms
(e.g., tablet versus capsule; immediate
release dosage form versus controlled
release dosage form).Strengths.
Bioequivalent Chemical Pharmaceutical Therapeutic
Equivalent equivalents Equivalent

Same drug same labelled Same drug same

(active ingredient chemical Same dose therapeutically
or chemical substance as an Same dosage active ingredient
moiety) active ingredient form elicit identical
Same dose in the same Same pharmacological
Same dosage amount disintegration effects and can
Reaches to blood time control the
circulation with Same dissolution disease to the
same rate and time same extent.
same extent Same purity
Same uniformity
of contents
 Introduction to
Biopharmaceutics ....
• Generic Equivalent or "generically
equivalent" means a drug that has an
identical amount of the same active
chemical ingredients in the same dosage
form, that meets applicable standards of
strength, quality and purity according to the
United States pharmacopeia or other
nationally recognized compendium and
that, if administered in the same amounts,
will provide comparable therapeutic effects.
 Introduction to
Biopharmaceutics ....
• Volume of distribution:
• A volume that must be considered in estimating
the amount of drug in the body from the
concentration of drug found in the sampling
compartment.
• The volume of distribution is the apparent
volume (VD) in which the drug is dissolved after
reaches equillibrium.
• It is distribution of a drug between plasma and
rest of the body after oral and parenteral dosing
• Because the value of the volume of distribution
does not have a true physiologic meaning in
terms of an anatomic space, the term apparent
volume of distribution is used. Or may be all of
the parts of body equilibrated with the drug do
not have equal concentration.
 Introduction to
Biopharmaceutics ....
Volume of distribution
• The amount of drug in the body is not
determined directly.
• Instead, blood samples are collected at
periodic intervals and the plasma portion of
blood is analyzed for their drug concentrations.
• The Vd relates the concentration of drug in
plasma (Cp) and the amount of drug in the
body (Db), as in the following equation: Db = Vd
Cp
 Introduction to Biopharmaceutics ....

Half life:
The time taken for the concentration of
the drug in the plasma or the total
amount in the body reduced by one
half or 50 % of initial dose