This presentation summarizes key concepts regarding bioavailability and bioequivalence studies. It defines bioavailability as a measure of the rate and amount of drug reaching systemic circulation following administration of a dosage form. Absolute bioavailability compares intravenous and oral administration, while relative bioavailability compares oral formulations. The objectives of these studies are outlined. Methods of measuring bioavailability through pharmacokinetic methods like plasma level time studies and urinary excretion studies are described. Bioequivalence ensures two dosage forms reach systemic circulation at the same rate and extent. Study designs for in vivo and in vitro bioequivalence experiments are discussed, including completely randomized, randomized block, repeated measures, cross-over, and Latin square designs.

1. Presentation on
Bioavailability & Bioequivalence Studies
Presented By :- Vishal Shelke
M.Pharm – I
Guided By :- R. Chavan
Department of Pharmaceutics
PDEA’s SGRS College of Pharmacy Saswad

2. Contents :-
 Definitions
 Objectives of Bioavailability studies
 Methods of Bioavailability measurement
-- Pharmacokinetic methods:
-- Pharmacodynamic methods:
 Bioequivalence experimental study designs
1. Completely randomized designs
2. Randomized block designs
3. Repeated measures, cross over, carry-over designs
4. Latin square designs

3. Bioavailability:
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.
Absolute bioavailability:
When systemic availability of a drug administered orally
is determined in comparison to its I.V. administration,
denoted by F.
Relative bioavailability:
When systemic availability of a drug after oral
administration is
Compared with that of oral standard of the same drug
( Solution or suspension ) and denoted by Fr.

4. Objectives of Bioavailability Studies :-
It is important in the
 Primary stages of development of dosage form of new drug
entity to find its therapeutic utility.
 Determination of influence of excipients on absorption.
 Development of new formulations of existing drugs.
 Control of quality of drug products and influence of
processing factors , storage and stability on absorption.
 Comparison of drug in different dosage forms or same
dosage form of different manufacturer.

5. Methods of Bioavailability Measurement :-
Phamacokinetic Method
1. Plasma level time studies:
most reliable method of choice comparison to urine data method
Single dose: serial blood samples collection – 2-3 half lifes
Plot concentration vs time graph
• For I.V. Sampling started within 5 min and subsequent samples at
15min intervals
• For oral dose at least 3 points taken on absorption curve ( ascending
part)

6. Parameters considered important in plasma level time studies
1. Cmax : It is peak plasma concentration. It increases with dose as
well as increase in rate of absorption.
2. Tmax: The peak time at which Cmax atended.
3. AUC: Area under curve explains about amount of drug.

7. 2. Urinary excretion studies:
This method is based on the principle that the urinary excretion of
unchanged drug is directly proportional to the plasma concentration of drug.
It can be performed if
- At least 20% of administered dose is excreted unchanged in urine.
- Drugs that extensively excreted unchanged in urine eg. Thiazide diuetics
- Drugs that have urine as site of action eg. Urinary antiseptics like
nitrofurontoin.
Steps involved :
• collection of urine at regular intervals for 7 half lifes.
• Analysis of unchanged drug in collected sample.
• Determination of amount of drug at each interval and cumulative as well.
Following Criteria's must be followed
• At each sample collection total emptying of bladder is necessary.
Frequent sampling is essential in the beginning to compute correct rate of
absorption.
• The fraction excreted unchanged in urine must remain constant.

8. 1. Acute pharmacological response:
When bioavailability measurement by pharmacokinetic methods is
difficult, inaccurate or non reproducible this method is used. Such as
ECG, Pupil diameter etc.
It can be determined by dose response graphs. Responses measure for
at least 3 half lifes.
2. Therapeutic response:
This method is based on observing clinical response in patients.
Drawbacks :
- The physiological status of subject assumed that does not change
significantly over duration of study.
- If multiple dose protocols are not involved. Patient receive only
single dose for few days or a week
- The patient s receiving more than one drug treatment may be
compromised due to drug-drug interaction.
Pharmacodynamic methods

9. Bioequivalence Studies
It is a relative term which denotes that the drug substance in
two or more identical dosage forms, reaches the systemic
circulation at same relative rate and relative extent.
Types of Bioequivalence studies :
1. In Vivo Bioequivalence studies
2. In Vitro Bioequivalence studies

10. In Vivo Bioequivalence studies :-
The following sequence of criteria is useful in assessing the
need for in vivo studies.
a. Oral immediate release products with systemic action
- Indicated for serious conditions requiring assured response.
- Narrow therapeutic margin.
Unfavourable physiochemical properties e.g., Low solubility,
meta stable modifications, instability etc.
b. Non Oral immediate release products
c. Modified release products with systemic action.

11. 2. In Vitro Bioequivalence studies :-
In comparative in vitro dissolution studies. In vivo
bioequivalence under certain circumstances called as
biowaivers
The drug product differs only in strength of the active
substances it contain, provided all the following conditions
hold-
• The drug product has been slightly reformulated method
has been slightly modified.
• The drug product is in the form of solution or solubilised
form (eg., elixir, syrup, tincture etc.,
• In vitro dissolution rate of the new products is equivalent
with that of the already approved medicinal product.
Topical administration (Cream, ointment gel) for local
effect. Oral administration but intended to be absorbed.

12. Bioequivalence Experimental study design:
1. Completely randomisation
2. Randomised block designs
3. Repeated measures, cross over and carry over designs
4. Latin square designs
1. Completely randomisation
In a completely randomised design, all treatments are
randomly allocated among all expermental subjects.
Method of Randomisation: Subject with the same number of digits
Advantages: The design is extremely easy to construct Accommodate
number of treatments and subjects.
Disadvantages: The situations in whcih there are relatively few
treatments .

13. 2. Randomised block design :-
First subject are homogenous groups called blocks and
the treatments are then assigned at random with in the blocks.
Method of Randomisation:- Subjects having back ground
characteristics are found as blocks.
Advantages: Accomodate any number of treatments Treatment need
not have equal sample size Statistical analysis is relatively simple.
Disadvantages: Missing observations with in a block require more
complex analysis. The degree of freedom of experimental error are
not a large.

14. 3. Repeated measures :- cross over and carry over
designs
The Randomised block design in which the same subject
serves as a block. The administration of two or more
treatments one after the other in a specified order to the
same group of patients is called a cross over design. To
prevent carry over effect one must always allow for a
wash out period during which most of the drug is
eliminated form the body generally about 10 elimination
half lives.
Example: Clinical trials to monitor safety and side
effects.

15. Method of Randomisation.
Complete randomisation is used to randomise the order
of treatments for each subject.
Advantage:
It provides good precision for comparing treatments because
variability b/w subjects. It is economic on subjects. The
interest in the effects of a treatment over time, it is easy to
observe the same subject at different points.
Disadvantage:
There may be an order effect, which is connected with the
position in the treatment order. There may be a carry over
effects, which is connected with the preceding treatment.

16. 4. Latin square designs :-
Completely randomised design, randomised block
design and repeated measures design are experiments
where the person / subject / volunteer remains on the
treatment from the start of the experiments untill the end
are called as continuous trail.
A latin square design is a two factor design with one
observation in each cell. A latin square is called standard if
the first row add the first column consist of the r letters in
alphabetical order.

17. References :-
1. Biopharmaceutics and pharmacokinetics – A Treatise,
D. M. Brahmankar, Sunil B.Jaiswal. Vallabh prakashan IInd
edition 315-366
2. Internet Sources

18. Also available on Youtube
Youtube :- https://youtube.com/vishalshelke99
Instagram :- https://instagram.com/vishal_stagram

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