2. BIOAVAILIBILITYBIOAVAILIBILITY ??
īIs the rate and extent (amount) of absorption of
unchanged drug from its dosage form.
īBioavailable fraction: administered dose that enters
the systemic circulation
f = bioavailable dose
administered dose
3. Objectives:-
īDevelopment of a suitable dosage form
īDevelopment of new formulation
īControl of quality of a drug
īInfluence of recipients , patient related factors ,
interaction with other drugs
4. Types Of Bioavailability
Are of 2 types:-
ī Absolute bioavailability
systemic availability of a drug administered orally is
determined in comparison to its intravenous
administration
ī 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
īRequires collection of fewer blood samples
īBetter evolution of control released drug is possible
īMore accurate
īLess 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
ī 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
ī urinary excretion of unchanged drug is directly
proportional to the plasma concentration of drug
ī studies is carried for extensively excreted
unchanged drugs in the urine methodology
ī collection of urine samples at regular intervals for 7
biological half lives analysis of unchanged drug in
the sample
ī total emptying of bladder is necessary
ī parameters used are (dx/dt)max , (tu)max , xu
12. Pharmacodynamic studies
Acute pharmacologic response
īŧ This Include ECG readings, pupil diameter is related
to time course of a given drug.
īŧPharmacologic effect âtime curve is used
īŧAt least 3 biologic half lives are taken
Therapeutic response
īObserving the clinical response to a drug formulation
given to patients
13. In vitro studies
īFor this dissolution studies is done
īRotating paddle apparatus is used
īDrug is dissolved in 250ml of aqueous media at ph
of 1-7.5
īSpeed of paddle should be 100 rpm
īMedia used having ph-6.8,in 0.1n hcl
īTemperature 37 degree Celsius.
14. Bioquivalence
īRelative 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
īShould be done for the comparison of the 2
medicinal products having the same active
substance
īIn order to ensure clinical performance of such
drugs.
Cases where bioequivalence studies not
required
ī drug is gas
ī drug is administered parentally
ī drug is in form of inhalation
16. Bioquivalence studies
Terms used in bioequivalence studies
īBioequivalence
īChemical Eqivalence
īPharmaceutical equivalents
īTherapeutic equivalents
17.
18. Methods used in bioquivalence
studies
īPharmacokinetic methods
īPharmacodynamic methods
īIn âvitro studies
īLatin square design cross over
19. Cross over latin design
īA crossover study (also referred to as a crossover
trial) is a study in which subjects receive a
sequence of different treatments (or exposures).
ī crossover studies can be observational studies,
many important crossover studies are controlled
experiments.
īcrossover 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
īDetails of analytical method validation
īComments of chief investigator regarding the data
īClinical data according to GCP
īAnalytical data of volunteer plasma samples
īCopy of final report
22. Study report
īTable of contents
īTitle of study
īName of responsible investigator
īSite of the study
īDates and period in which trials are conducted
īName and batch number of products
īResults of pharmaceutical tests
īDemographic data of subjects
īNames and address of subjects
īDetails of dropout and withdrawal of subjects
īReports of protocol violations
īDetails of how pharmacokinetic parameters were
calculated
īDocuments related to statistical analysis
23. Facilities for conducting the studies
The study site must have the following
īŧAn investigator
īŧClinical pharmacological unit
Qualified and trained personnel to perform
the following
īŧData handling and interpretation
īŧDocumentation and report preparation
īŧLaboratory management
īŧQuality assurance of all operations in the centre
24. Maintainance of records
īShould be maintained by the sponsor for atleast 2
years after the expiration of batch of drug
Retention OF BA/BE
Samples
īShould 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.