Bioavailability

BIOAVAILABILITY
PAD.DR.D.Y.PATIL COLLEGE OF PHARMACY
AKURDI PUNE.
PRESENTED BY
MR.VILAS KAMBLE
M.PHARM.II SEM.
GUIDED BY
MRS. DR.USHA SHINDE

CONTENT
Introduction
Objective
Consideration in bioavailability
Measurement of bioavailability
References

INTRODUCTION
 The therapeutic effectiveness of a drug
depends upon the ability of dosage
form to deliver the medicament to its
site of action at a rate and attribute of a
dosage form.
API in
dosage form
API in free
form
API in
systemic
circulation
Therapeutic
action

INTRODUCTION
 Definition:-
The rate and extent (amount) of
absorption of unchanged drug from its
dosage form.

INTRODUCTION
 Bioavailability depends upon three
major factor.
Pharmaceutical
factor
Patient related
factor
Rout of
administration

INTRODUCTION
Topical
Rectal
Oral
Parenteral

INTRODUCTION
 However, for reasons of stability and
convenience, most drug are
administered orally. In such case the
dose available to the patient, called as
bioavailable dose.
 Bioavailable fraction:-
Bioavailable dose
=
Administered dose

OBJECTIVE
 In R&D of suitable dosage form.
 Determination of influence of excipient,
patient related factors and drug
interaction on the efficiency of absorption.
 Development of new formulation of
existing drug.
 QC of dosage form.
 Comparison of BA of a drug substance
from different dosage forms or from the
same dosage form produce by different
manufacture.

CONSIDERATION IN BIOAILABILITY STUDY
DESIGN
Absolute vs. relative
Absolute bioavailability (F):-
When the systemic BA of a drug
administer orally is determine to its i.v
administration, it is called as absolute BA.
o Importance:-
To characterize drug’s inherent
absorption properties from the i.v site.

DESIGN
Relative bioavailability (Fr):-
When the systemic availability of
a drug after oral administration is
compare with that of an oral standard of
the same drug it is refer to as
comparative or relative bioavailability.
o Importance:-
Used to characterize absorption of
drug from its formulation.

DESIGN
Single dose vs. Multiple Dose
studies.
The dose to be administered
for a bioavailability study is determine
by preliminary clinical experiment.

DESIGN
Advantages
It is very conman
study
Less exposure to
drug
Less tedious
Disadvantages
Difficult to produce
steady state
characteristics of drugs
Long sampling period
are necessary.
 Single dose study

DESIGN
Advantages
More accurate
Easy to predict peak
characteristics
Require collection of fewer
blood sample
Can be ethically performed in
patient
Small inter-subject variability is
observed.
Multiple dose study

DESIGN
Disadvantages
Require more time.
Tedious.
Poor compliance by subject
Greater exposure of subject to
the test drug.

Design
Human volunteers-Healthy Subject
vs. Patient
Ideally, the bioavailability study
should be carried out in patients for
whom the drug is intended to be used.

Design
Patients
Will be benefited
from the study
Reflects better
the therapeutic
efficacy of
drug.
Drug absorption
patterns can be
evaluated
Avoid the ethical
quandary of
administering
drug to healthy
subject.

MEASUREMENT OF BOAVAILABILITY
Measurement
of
bioavailability
Pharmacokin
etic method
Plasma level
time studies
Urinary
exceretion
studies
Pharmacody
namic
method
Acute
pharmacologi
cal response
Therapeutic
response

Pharmacokinetic method:-
These method are based on
the assumption that the
pharmacokinetic profile reflects the
therapeutic effectiveness of a drug.
Thus, these are indirect methods

Plsma level time studies:-
• Most common type of human bioavailability
studies.
• Based on the assumption that there is a
direct relationship between the
concentration of drug in blood or plasma
and the concentration of drug at the site of
action.
• Following the administration of a single
dose of a medication, blood samples are
drawn at specific time intervals and

 Following the administration of a single
dose of a medication, blood samples are
drawn at specific time intervals and
analyzed for drug content.
 A profile is constructed showing the
concentration of drug in blood at the
specific times the samples were taken.
 Bioavailability is generally assessed by
the determination of following three
parameters.

 Two dosage form having same plasma
level time profile should result in identical
therapeutic activity.
 Plot of concentration vs. time of sample
collection to obtained a plasma level
time profile

0
10
20
30
40
50
60
0 10 20 30 40 50 60
TIME IN MIN.
CONCEOFDRUGIN
MICROGRAMPERML

• Bioavailability is generally assessed by
the determination of following three
parameters.
Cmax
Tmax
AUC

Cmax: (Peak plasma drug
concentration)
 Maximum concentration of the drug
obtained after the administration of single
dose of the drug.
 Expressed in terms of μg/ml or mg/ml.
Tmax: (Time of peak plasma conc.)
Time required to achieve peak
concentration of the drug after
administration.
 Gives indication of the rate of absorption.
 Expressed in terms of hours or minutes.

AUC: -
Is the measurement of the extent of the
drug bioavailability
 It is the area under the drug plasma
level-time curve from t =0 & t = ∞, and
is equal to the amount of unchanged
drug reaching the general circulation
divided by the clearance.

The extent of bioavailability can be
determined by the following equations:
 For single dose study
For multiple dose study:

Urinary Excretion Studies:
 Urinary excretion of unchanged drug is directly
proportional to plasma concentration of drug.
 Thus, even if a drug is excreted to some extent
(at least 10 to 20%) in the urine, bioavailability
can be determined.
e.g.: Thiazide diuretics, Sulphonamides.
• Method is useful when there is lack of sufficiently
sensitive analytical technique to measure drug
concentration.
 Noninvasive method, so better patient
compliance.

 Three Important Parameters in urine
excretion data for single dose study:
(dxu/dt)max (tu)max
Xu∞

Plot of urinary excretion rate Vs time

(dxu/dt)max :(Maximum urinary excretion
rate)
• Its value increases as rate and/or extent
of absorption increases.
• Obtained from peak of plot between rate
of excretion versus midpoint time of
urine collection period.
(tu) max:
• Time for maximum excretion rate

• Its value decreases as absorption rate
increases.
• Analogues of tmax of plasma level data.
Xu
∞:Cumulative amount of drug
excreted in urine
• Related to AUC of plasma level data.
• It increases as the extent of
absorption increases.

The extent of bioavailability is
calculated from equation :
For single dose study:
 For multiple dose study:

Acute Pharmacologic Response
Method:
• When bioavailability measurement by
pharmacokinetic method is difficult, an
acute pharmacologic effect such as
effect on pupil diameter, EEG & ECG
readings related to time course of
drug.
• Bioavailability can then be determined
by construction of pharmacological
effect- time curve as well as dose
response graphs.

Disadvantage:
• It tends to be more variable.
• Observed response may be due to an
active metabolite whose concentration
is not proportional to concentration of
parent drug.

Therapeutic Response Method:
• This method based on observing the
clinical response to a drug formulation
given to patient suffering from disease.

Drawbacks: The major drawbacks of
this method is that quantitation of
observed response is too improper to
allow for reasonable assessment of
relative bioavailability between two
dosage forms of the same drug.
E.g.: Anti-inflammatory
drugs.
 Many patients receive more than one
drug

 Drug dissolution studies may under
certain conditions give an indication of
drug bioavailability.
 Dissolution studies are often
performed in several test formulations
of the same drug.

 The test formulation that demonstrates
the most rapid rate of drug
bioavailability in-vitro will generally
have the most rapid rate of drug
bioavailability in-vivo.
 The FDA may also use the other in-
vitro approaches for establishing
bioequivalence.
Ex: Cholestyramine resin.

REFRENCES
• Brahmankar .D.M , Sunil Jaiswal,
“Biopharmaceutics and
Pharmacokinetics-A Treatise”, Second
edition, page no. 236-337.
• V Venkateshwarlu,
“ Biopharmaceutics &
pharmacokinetics’’
page no. 403-416.

Bioavailability

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