BIOAVAILABILITY

-: Presented By :-
Amruta S. Sambarekar
1st Year M.Pharm
Dept. of Pharmaceutics
M M C P, BELGAUM
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 CONTENTS

 Concept of Bioavailability

 Objectives of Bioavailability Studies

 Considerations in Bioavailability
Studies

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 INTRODUCTION

Bioavailability is defined as a measure, of

the rate and amount of drug, which reaches
the systemic circulation unchanged
following the administration of a dosage
form.

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 Cont….
In other words, it is the fraction of
administered dose that actually reaches
the systemic circulation in contrast to that
stated on the label.

 Bioavailability is usually determined by

comparing the rate and extent of
absorption of drug from the formulation
under evaluation, to the data of a
reference standard.
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 Cont….
If the reference standard is an IV dose, it is
referred as Absolute Bioavailability. If
the reference standard is any other dosage
form than IV it is referred as Relative
Bioavailability.

Reference standard can be IM injection,

oral solution or a fine suspension.

Bioavailability usually ranges from 0 to 1.

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 Cont….
An absolute bioavailability of 1 (or 100% )
indicates complete absorption.

Relative bioavailability of 1 (or 100%)

implies that bioavailability of drug from
both the dosage form is the same but does
not indicate the completeness of
absorption.
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Bioavailability of drug from dosage form
depends upon following,

- Properties of the drug

- Important physiological factors
- Characteristics of the dosage form

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 Bioavailability Studies

Two types are there, The first type

involves an assessment of the
bioavailability of a new drug formulation.

The second type study involves a

comparison of a test formulation with that
of a reference standard dosage form that is
proved to have a therapeutic safety and
efficacy.
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 Objectives

Primary stage of development for suitable

dosage form for a new drug entity.

Determination of influence of excipients,

patient related factors and possible
interaction with other drugs on the
efficiency of absorption.
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 Cont….

For a approved drugs to develop a new

dosage form or to improve an existing
dosage form.

To find out the influence of

physicochemical properties of drug and
dosage form on biological performance of
the drug.
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 Cont….

Useful in determining the safety and

efficacy of the drug product.

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 Considerations in Bioavailability
Studies

 Selection Of Subjects

 Study Design

 Washout Period

 Single Vs Multiple- Dose Study Design

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 Study Conditions

 Pharmacological Effects of Metabolite

 Assay Method

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 Selection Of Subjects
A number of factors such as health, age,
weight, enzyme status and number are
concern.

It is better to have the subjects of similar

kinetics to avoid major variations.

Health : Subjects should be of great health

that is ascertained by various biochemical
and medical examination. 14
Age :
Elderly and children have different
kinetics to adults. Subjects between 18 – 35
years are preferred.

Number :
Number of participants should be kept
minimum required for carrying out a
reliable, well designed study.

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 Weight :

The apparent volume of distribution is

usually proportional to weight in subjects
of normal weight and height.

However, in overweight and underweight

Vd may be different. Hence, to better
match the subject , normal weights are
preferred. Usually 140-200lb

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 Enzyme Status :

 Enzyme activity can be altered by altered

kinetics of the drug in case of smokers or
subjects taking other drugs leading to
drug-drug interaction.

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 Study Design
Usually, a complete cross over study
design is used. With this design each
subject receives all products with a
washout period between each dose
administration.

This is a Latin square crossover design

where each subject receives each drug
product only once . Here each subject act
as his own control and subject to subject
variation is reduced. 18
 Washout Period :

 The time interval between two treatments

is called “washout period”.

It is required for the elimination of the

administered dose of a drug so as to avoid
a carryover effect

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 Cont….
Usually, a period of 10 half-lives should be
allowed between two treatments ensuring
elimination of 99.9% of the administered
dose.

The number of washout period depends

upon the type of crossover study design
used and number of formulations to be
evaluated.
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 Cont….
In case of Digitoxin,

 Half –life : 6 to 9 days

 Study design :Latin square crossover
design for four formulations.
Duration : 1 year

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Single Vs. Multiple- Dose Study Design

Single- Dose Studies Recommended For

Dosage forms that are to be evaluated only

for bioequivalence purpose.

Dosage forms meant for a single dose

administration for a therapeutic benefit
such as analgesic for relief of headache.

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 Multiple Dose Studies Recommended For

Dosage forms designed to achieve special

release profiles. e.g. time-release products,
enteric-coated preparations.

Drugs undergoing first pass metabolism.

Special dosage regimens such as Loading

dose.
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Study conditions
Subject should be maintained on a
uniform diet and none of them should
have taken any drug at least one week
prior to the study.

Before the commencement of study it is

necessary to define the study condition
such as fasting period before the
administration, time period after drug
product administration, during which
fasting is continued. 24
Cont….

In general studies are carried out on

subjects fasted overnight.

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 Pharmacological Effects of
Metabolites

Bioavailability measurement is based on

the unchanged drug.

Drugs having biologically active

metabolites, their concentration in
systemic circulation can influence greatly
the therapeutic efficacy of the drug.
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 Cont….
It was found especially significant for
drugs which exhibits first pass metabolism
during pre-absorptive phase.

Phenacetin has more side effects than, its

metabolite acteaminophen, which is also
pharmacologically active form.

In case of aspirin its metabolite salicylic

acid is pharmacologically inactive and
exhibits serious toxicity.
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 Cont….
Based on above findings, it is good
practice in bioavailability studies to
examine the presence of major metabolites
in blood and urine, to determine their
concentration and, if possible,
pharmacological activity of each.

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 Assay method

The analytical method used to quantitate

the levels of drug and/or its metabolites
must be selective e.g., for the unchanged
drug in presence of its metabolites.

It must be sensitive enough to measure the

expected low drug levels in the samples
collected last.
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 REFERENCE
 “Text Book Of Biopharmaceutics &
Pharmacokinetics”, Dr. Shobha Rani R. Hiremath.
Pg no. 31-35.

 “Biopharmaceutics & Pharmacokinetics”

Venkatesh Pg no. 331, 336-338.

 “Biopharmaceutics & pharmacokinetics”,

D.M.Brahmankar, S.B.Jaiswal, Pg.no. 283.

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