Bioavailability is defined as the fraction of an administered drug dose that reaches systemic circulation. It is determined by comparing the rate and extent of absorption of a test formulation to a reference standard, usually an intravenous dose. Key considerations in bioavailability studies include selecting appropriate subjects, study design such as single vs multiple dose studies and washout periods, and ensuring the analytical method can detect drug and metabolite levels. The goal is to understand how formulation characteristics impact the biological performance of the drug.

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

2. CONTENTS
 Concept of Bioavailability
 Objectives of Bioavailability Studies
 Considerations in Bioavailability
Studies
2

3. 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.
3

4. 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.
4

5. 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.
5

6. 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.
6

7. Bioavailability of drug from dosage form
depends upon following,
- Properties of the drug
- Important physiological factors
- Characteristics of the dosage form
7

8. 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.
8

9. 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.
9

10. 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.
10

11. Cont….
Useful in determining the safety and
efficacy of the drug product.
11

12. Considerations in Bioavailability
Studies
 Selection Of Subjects
 Study Design
 Washout Period
 Single Vs Multiple- Dose Study Design
12

13.  Study Conditions
 Pharmacological Effects of Metabolite
 Assay Method
13

14. 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

15. 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.
15

16. 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
16

17. 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.
17

18. 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

19. 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
19

20. 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.
20

21. Cont….
In case of Digitoxin,
 Half –life : 6 to 9 days
 Study design :Latin square crossover
design for four formulations.
Duration : 1 year
21

22. 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.
22

23. 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.
23

24. 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

25. Cont….
In general studies are carried out on
subjects fasted overnight.
25

26. 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.
26

27. 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.
27

28. 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.
28

29. 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.
29

30. 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.
30

31. !! !
u !
y o
nk
ha
T 31