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
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
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
17.
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
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.