1. BY:- MUKESH JAISWAL
BIOAVAILABILITYBIOAVAILABILITY
&&
BIOEQUIVALANCEBIOEQUIVALANCE

2. BIOAVAILIBILITYBIOAVAILIBILITY ??
Is the rate and extent (amount) of absorption of
unchanged drug from its dosage form.
Bioavailable fraction: administered dose that enters
the systemic circulation
f = bioavailable dose
administered dose

3. Objectives:-
Development of a suitable dosage form
Development of new formulation
Control of quality of a drug
Influence of recipients , patient related factors ,
interaction with other drugs

4. Types Of Bioavailability
Are of 2 types:-
 Absolute bioavailability
systemic availability of a drug administered orally is
determined in comparison to its intravenous
administration
 Relative bioavailability
systemic availability of a drug after oral
administration is compared with that of the same
drug

5. Methods of enhancing
bioavailability
Micronization
Use of surfactants
Use of salt forms
Selective adsorption on insoluble carriers
Solvent deposition

6. Above graph shows the comparison of drug
concentration in blood due to different dosage
forms

7. BIOAVAILABILITY STUDIES
Single dose vs. multiple dose studies
Requires collection of fewer blood samples
Better evolution of control released drug is possible
More accurate
Less sensitive analytical method can be used

8. Healthy human subjects vs.
patients
Advantages of patient Advantages
of healthy subjects
1. Benefit 1.Standard of drugs
2.Therapeutic efficacy
3.Drug absorption
Drawbacks of patients
1. Drug absorption modify

9. Measurement Of Bioavailability
Studies
1.> Pharmacokinetic methods
 1.plasma level time studies
 2. urinary excretion studies
2.>Pharmacodynamic methods
 1.acute pharmacologic response
 2.therapeutic response
3.>in vitro studies

10. Pharmacokinetic studies
Plasma level time studies
 Principle
The plama level time profile of a perticular drug will not super
impose by the other drug profile thus result in identical therapeutic
response.
There are three parameters used in plasma time studies:-
1. Cmax, 2. Tmax & 3. AUC
Methodology
single dose study multiple dose study
1. collection of blood samples 1. collection of blood samples
for 2-3 half lives after drug for at least 5 half lives
administration
2. analysis of drug concentration
3. plotting of graph b/w conc. Of
drugs and time

11. Urinary excretion studies
Principle
 urinary excretion of unchanged drug is directly
proportional to the plasma concentration of drug
 studies is carried for extensively excreted
unchanged drugs in the urine methodology
 collection of urine samples at regular intervals for 7
biological half lives analysis of unchanged drug in
the sample
 total emptying of bladder is necessary
 parameters used are (dx/dt)max , (tu)max , xu

12. Pharmacodynamic studies
Acute pharmacologic response
 This Include ECG readings, pupil diameter is related
to time course of a given drug.
Pharmacologic effect –time curve is used
At least 3 biologic half lives are taken
Therapeutic response
Observing the clinical response to a drug formulation
given to patients

13. In vitro studies
For this dissolution studies is done
Rotating paddle apparatus is used
Drug is dissolved in 250ml of aqueous media at ph
of 1-7.5
Speed of paddle should be 100 rpm
Media used having ph-6.8,in 0.1n hcl
Temperature 37 degree Celsius.

14. Bioquivalence
Relative term which denotes that the drug substance
in 2 or more identical dosage forms ,reaches the
systemic circulation at the same relative rate and to
the same relative extent

15. Objectives
Should be done for the comparison of the 2
medicinal products having the same active
substance
In order to ensure clinical performance of such
drugs.
Cases where bioequivalence studies not
required
 drug is gas
 drug is administered parentally
 drug is in form of inhalation

16. Bioquivalence studies
Terms used in bioequivalence studies
Bioequivalence
Chemical Eqivalence
Pharmaceutical equivalents
Therapeutic equivalents

18. Methods used in bioquivalence
studies
Pharmacokinetic methods
Pharmacodynamic methods
In –vitro studies
Latin square design cross over

19. Cross over latin design
A crossover study (also referred to as a crossover
trial) is a study in which subjects receive a
sequence of different treatments (or exposures).
 crossover studies can be observational studies,
many important crossover studies are controlled
experiments.
crossover designs have "balance", which means
that all subjects should receive the same number of
treatments and that all subjects participate for the
same number of periods

20. Advantages
Minimizes intersubject variability
Minimizes the variations due to time effect.
Disadvantages
Takes a long time
Study becomes difficult when there are number of
formulations to be tested

21. Documentation for conduction ofDocumentation for conduction of
studistudieses
Details of analytical method validation
Comments of chief investigator regarding the data
Clinical data according to GCP
Analytical data of volunteer plasma samples
Copy of final report

22. Study report
Table of contents
Title of study
Name of responsible investigator
Site of the study
Dates and period in which trials are conducted
Name and batch number of products
Results of pharmaceutical tests
Demographic data of subjects
Names and address of subjects
Details of dropout and withdrawal of subjects
Reports of protocol violations
Details of how pharmacokinetic parameters were
calculated
Documents related to statistical analysis

23. Facilities for conducting the studies
The study site must have the following
An investigator
Clinical pharmacological unit
Qualified and trained personnel to perform
the following
Data handling and interpretation
Documentation and report preparation
Laboratory management
Quality assurance of all operations in the centre

24. Maintainance of records
Should be maintained by the sponsor for atleast 2
years after the expiration of batch of drug
Retention OF BA/BE
Samples
Should be retained by organization for period of 3
years after the completion of studies or 1 year after
the expiration of batch ,whichever is early.

25. Thank you
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